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. 

August 2014
Everything You Need to Know About Medical Marijuana and Parkinson’s Disease

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

June 2014
Is light therapy a potential treatment modality in Parkinson’s disease?

May 2014
How does the most common genetic cause of Parkinson’s Disease (LRRK2) cause Parkinson’s disease and could it be used to help develop a better therapy?

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
Should I take Inosine to Raise my Uric Acid Levels and Treat my Parkinson’s Disease?

December 2013
Could Fungus and Mold be an Important Contributor to Parkinson’s Disease?

November 2013
Pimavanserin and the Hope for a Better Drug for Hallucinations and Psychosis in Parkinson’s Disease

October 2013
Halting of the Creatine Study

September 2013
The Importance of Identifying and Treating Caregiver Strain

August 2013
Putting Parkinson’s Disease Information into the Palm of Your Hand: Parkinson’s Enters the Smartphon

July 2013
What Parkinson’s Disease Patients Need to Know about H. Pylori Gastrointestinal Infections

June 2013
A2A Receptor Antagonists and Parkinson’s Disease Treatment

May 2013
Another Setback for Trophic Factor Treatment in Parkinson's Disease

April 2013
IPX066 and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations

March 2013
The Weather Forecast for Parkinson’s Disease Calls for Worldwide Economic Storm

February 2013
Defeating the Barriers to Implementing Exercise Regimens in Parkinson’s Disease Patients

January 2013
When should you start medication therapy for Parkinson’s disease?

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
Watch out for Unexpected Obstacles if You Use a Cueing Strategy to Break Freezing of Gait in Parkinson’s Disease

February 2012
Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient

January 2012
Are Blood Tests for Parkinson’s Disease on the Horizon?

December 2011
Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step

November 2011
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression

October 2011
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team

September 2011
Scientists say Research on Brain Proteins Involved in Parkinson’s Disease is “Shaping” Up

August 2011
Who Actually Takes Care of Most of the Parkinson’s Patients Worldwide: The Need for Education and the Parkinson’s Toolkit

July 2011
If you are Dizzy or Passing Out, it could be Your Parkinson’s Disease or Parkinson’s Disease Medications

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

May 2011
Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease

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
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management

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
Time for Comprehensive Care Networks for PD

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
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)

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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