Your current research aside, what are some of the factors in favor of GPi DBS vs. STN DBS and vice versa? How might surgeons and physicians have made the treatment decision?
Dr. de Bie and Dr. Odekerken: Before the Veterans Administration Cooperative DBS Study was published, surgeons and physicians have mostly made the decision for either bilateral GPi or STN DBS based on cohort studies and one small randomized controlled trial (RCT).1, 2 Since the majority of research concerned STN DBS, more reports of cognitive, mood and behavioral side effects were published for this nucleus. Therefore, some DBS teams preferred GPi DBS for the patients that already had minor cognitive, mood or behavioral issues. Also, GPi DBS leads to a direct reduction of dyskinesias without reduction of dopaminergic medication.
STN DBS also reduces dyskinesias in the long run, but only after a reduction of dopaminergic medication. Again, this was a reason for some teams to perform GPi DBS in patients with debilitating dyskinesias.
How did the overall responses to each form of DBS in your study (The Lancet Neurology, Early Online) compare to previously reported findings or expert expectations?
Dr. de Bie and Dr. Odekerken: The debate on GPi DBS vs STN DBS has been ongoing since the 1990s. Most studies found an improvement an off-drug phase Parkinson’s disease motor symptoms of around 50 percent after STN DBS (measured with the Unified Parkinson’s Disease Rating Scale Motor Examination).1-5 The fewer studies on GPi DBS generally showed a less strong improvement with this intervention. 5-7
The Veterans Administration Cooperative DBS Study was the only large randomized controlled trial performed before the NSTAPS,8 which showed an improvement of around 25 percent after both bilateral GPi DBS and STN DBS. Most experts found the relatively small effect of STN DBS in this study rather surprising. Our findings are again in agreement with the results of a meta-analysis of cohort studies that showed a reduction of 52 percent on the UPDRS ME with STN DBS.9
Unexpectedly, the NSTAPS showed no large differences in effect on cognition, mood and behavior between GPi DBS and STN DBS.
Your study did not find significant differences in primary endpoints, but there were differences in secondary endpoints. Could you describe these differences and their potential relevance?
Dr. de Bie and Dr. Odekerken: The differences between GPi and STN DBS regarding motor symptoms and effects on disability in the off-drug phase are large. For example, a typical patient who scored 50 on the AMC Linear Disability Scale (ALDS) in off phase preoperatively would only just be able to have a shower independently. With an improvement of about 12 points (GPi group) the patient would be able to walk down a flight of stairs. However, with an improvement of 20 points (STN group), this patient would be able to visit a restaurant independently.
The other secondary outcome measures, whether or not statistically significant, also favored STN DBS. The results for dyskinesias were an exception. Patients received the same amount of levodopa to induce an on phase during the standardized assessment at 12 months as at baseline. However, because patients with STN DBS use less medication in daily life, they might have less severe dyskinesias than indicated by our measurements during the standardized assessments. In this respect, diaries showed similar reductions in off time as well as time that dyskinesias were present for GPi and STN DBS.
In our opinion, both the rather large and significant differences in off-drug phase and other statistically non-significant differences consistently favoring STN DBS are important findings.
What questions remain to be answered/explored regarding GPi vs. STN DBS?
Dr. de Bie and Dr. Odekerken: The most important question is: Do the effects observed in the NSTAPS last in the long term? Hence, we are currently following the patients up to five years post-operatively.
Possible findings could be: persistently better effect of STN DBS, equality of GPi DBS and STN DBS in the long run, or even GPi DBS as a better option after long term follow-up.
What is the take-home from your study? How is it changing your approach to patient care and how might your colleagues around the world interpret/ apply the findings?
Dr. de Bie and Dr. Odekerken: Since the NSTAPS study, our DBS teams have solely used STN DBS as a surgical treatment option for Parkinson’s disease because of the large differences in outcome between GPi DBS and STN DBS in the off-drug phase. Our study results do not support a specific scenario in which GPi DBS is still the preferred target for a patient with Parkinson’s disease.
- Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol 2005;62:(4):554-560.
- Follett KA, Weaver FM, Stern M et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 2010;362:(22):2077-2091.
- Deuschl G, Schade-Brittinger C, Krack P et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. [Erratum appears in N Engl J Med. 2006 Sep 21;355(12):1289]. N Engl J Med 2006;355:(9):896-908.
- Limousin P, Pollak P, Benazzouz A et al. Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord 1995;10:672-674.
- Rodriguez-Oroz MC, Obeso JA, Lang AE et al. Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up. Brain 2005;128:(Pt 10):2240-2249.
- Krause M, Fogel W, Heck A et al. Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus. Journal of Neurology, 2001 Apr 2001;70(4):464-470.
- Volkmann J, Allert N, Voges J, Sturm V, Schnitzler A, Freund HJ. Long-term results of bilateral pallidal stimulation in Parkinson’s disease. Ann Neurol 2004;55:(6):871-875.
- Odekerken VJ, van LT, Staal MJ et al. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol 2012.
- Kleiner-Fisman G, Herzog J, Fisman DN et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 2006;21 Suppl 14:S290-S304.