Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS

You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration.

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.*

Selected References

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 in Parkinson'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.

Posted: 7/9/2012 12:47:26 PM by Cathy Whitlock

Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun. 

June 2015
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May 2015
Leaps in Deep Brain Stimulation Technology

April 2015
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March 2015
Everything a Parkinson’s Disease Patient Needs to Know About the New Dopamine Pump

February 2015
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January 2015
More Evidence Linking Gut Bacteria to Parkinson’s Disease: A Guide for Patients

December 2014
Two New Therapies for Parkinson’s Disease Patients to get Excited About: Vaccines and Monoclonal Antibodies

November 2014
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October 2014
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September 2014
Deep Brain Stimulation for Parkinson’s Disease: NPF Congratulates Mahlon DeLong and Alim-Louis Benabid and Looks to a Bright Future in Human Neural-Network Modulation

August 2014
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July 2014
The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson's Disease

June 2014
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May 2014
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April 2014
An Update on DAT Scanning for Parkinson’s Disease Diagnosis

March 2014
Could Northera (Droxidopa) Be an Alternative Treatment for Low Blood Pressure and Passing Out Symptoms?

February 2014
The Dream of a Pill Free Existence and the Continuous Dopaminergic Pump for the Treatment of Parkinson's Disease

January 2014
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December 2013
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November 2013
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October 2013
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September 2013
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August 2013
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July 2013
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June 2013
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May 2013
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April 2013
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March 2013
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February 2013
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January 2013
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December 2012
Neurologist Care Reduces Hospitalizations in Parkinson's Disease

November 2012
A Victory in Court for Parkinson's Disease Patients who Require Ongoing Rehabilitative Therapies

October 2012
Given the recent FDA announcement about Mirapex (pramipexole), should I be worried about dopamine agonists?

September 2012
What about the new Parkinson’s Disease Vaccine? What should I know?

August 2012
Caffeine as a Potential Treatment for Parkinson’s Disease

July 2012
Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS

June 2012
A New Treatment for Parkinson’s Disease-Related Constipation

May 2012
Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs

April 2012
Measuring Quality and Assessing Depression in Parkinson's Disease

March 2012
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February 2012
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January 2012
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December 2011
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November 2011
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October 2011
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team

September 2011
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August 2011
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July 2011
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June 2011
How Will Group Visits for Parkinson’s Disease Fit into the Future of Parkinson’s Disease Care?

May 2011
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April 2011
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach

March 2011
Does it Matter if I Can’t Get Brand Sinemet?

February 2011
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?

January 2011
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

December 2010
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism

November 2010
Calling for the FDA to Revise the Eight Sinemet a Day Rule

October 2010
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease

September 2010
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts

August 2010
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research

July 2010
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June 2010
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?

May 2010
Is the PD SURG Trial Another Surge Forward for DBS Therapy?

April 2010
Cycling in PD in Those Who Can’t Walk: Is it Possible?

March 2010
New iPS Stem Cells for PD: What Does it Mean?

February 2010
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January 2010
Is Parkinson's Disease a Prion Disease?

December 2009
Parkinson's Disease Linked to Gaucher's Disease

November 2009
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies

October 2009
Is it Safe to Have an MRI with a DBS in Place?

September 2009
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August 2009
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?

July 2009
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms

June 2009
Keeping an Eye on Trials Important to the Parkinson's Disease Patient

May 2009
Increased Risk of Melanoma in Parkinson's Disease

April 2009
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients

March 2009
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?

February 2009
Is Exercise Effective Treatment and Protection Against PD?

January 2009
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?

December 2008
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?

November 2008
Update on Gene Therapy for Parkinson's Disease

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Each month, we will feature a new column by NPF's National Medical Director, Dr. Michael Okun, on the latest developments in Parkinson's disease research. Read the latest "What's Hot in PD?" below.

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