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 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.

One surprising fact in DBS technology is that the human deep brain stimulation (DBS) leads and the four shiny and tiny contacts on them have surprisingly not significantly changed for the last two decades.  One reason for the durability of DBS lead design has been the long-term beneficial effects of utilizing this simple approach.  There are however, compelling reasons to introduce new DBS lead designs into clinical practice.  Each target in the brain is a different size, and therefore the volume of electricity pumped into that target should be tailored to the appropriate region.  Additionally, there are structures and connecting pipes (fibers) that will require selective activation for an optimal response.  Finally, placing DBS leads accurately is not as easy as the general public may believe, and the ability to steer electrical current may enhance benefits and reduce stimulation-induced side effects.  In this month’s What Hot in Parkinson’s disease column we examine these new technologies.

Several companies have introduced different versions of DBS leads capable of steering and shaping the current.  Boston Scientific (8-contact lead, Vercise™ Implantable Pulse generator, Boston Scientific Corporation, Natick, MA) has a new lead in clinical trials that is capable of simultaneously activating multiple contacts at the same time, and allowing the physician or expert programmer to choose the percent of electrical current delivered at each contact on the DBS lead.  This DBS lead design was recently tested by Lars Timmermann and his colleagues in Germany.(1)  Additionally, there are twice as many contact points on this new DBS lead; eight as opposed to the standard four.  Eight contacts, and the ability to turn on one or all of the contacts (multiple source) and to shape the size of the current at each contact; collectively offers the possibility of a better benefit to side effect ratio however this will need to be demonstrated in formal studies.  The potential downside of this approach is that it may be harder for a general neurologist to program and the battery life of the device may be lessened by using multiple sources of current.  The company has attempted to answer these issues by providing a user friendly programming platform and a rechargeable device.  The system is now part of an ongoing clinical trial.

The Aleva company has a similar lead design to Boston Scientific and Dr. Pollo in Bern, Switzerland tested this new DBS lead design.  Dr. Pollo examined three different directions of stimulation and also used standard stimulation (all directions like a typical DBS lead now in clinical use).(2) In the original Aleva study, every patient with the exception of only one person showed a superior benefit favoring the current directional steering. These researchers also found they could get a therapeutic effect using less than half of the energy thereby reducing the battery drain.

A third Dutch company also recently introduced a new DBS lead design (Sapiens, now owned by Medtronic, Minneapolis, Mn).(3-5)  This DBS lead design lead is unique as it has 40 small circles (the active DBS contacts) spread over the length of the lead.  When I first saw the technology five years ago I dubbed the lead, “the leopard.”  The reason I called it the leopard is that the lead has a lot of spots all over it, and you can change, activate, and deactivate the spots in order to customize and shape the DBS current.  The company provides an easy to use interface for the clinician who can choose how to customize and to deliver the stimulation.  The lead has been successfully tested in monkeys by Jerry Vitek at the University of Minnesota, and in humans by Hubert Marteens and his team in Germany.

This year we also took another step forward in understanding the mechanisms underpinning the benefits of deep brain stimulation.  Phil Starr and his colleagues at the University of California San Francisco implanted DBS leads on top of the brain (cortex) and also deep into the brain in the subthalamic nucleus (the most commonly chosen target for deep brain stimulation).  Starr and his team found that in the motor cortex region (close to the surface of the brain) the cells were excessively synchronized to the brains native harmony or oscillation. When Cora De Hemptine on Starr’s team turned on the deep brain stimulator, the brain’s harmony became less synchronized and simultaneously the motor features of Parkinson’s disease improved.(6) The technology used by Starr’s lab was the Medtronic PC+S.

Another advance has been the realization that the DBS device may not actually need to be “on” all of the time.  Our group observed this phenomenon in a NIH study we recently performed with a graduate student named Nick Maling who went on to Case Western University in Cleveland Ohio.  When Nick was with us, we became interested in the idea that in Tourette syndrome patients could administer DBS on a limited duty cycle and that we could possibly still control tics.  In 3/5 of our original patients we demonstrated the proof of concept that we could capture tics by administering less that 2 hours of stimulation per day.(7,8)  Our group has also been experimenting with reprogramming the software on the DBS battery manufactured by Medtronic (the PC and SC) and delivering different shaped pulses to the brain.  In our preliminary study, which was performed by Dr. Umer Akbar before he departed for Brown University to start his own movement disorders program, we showed that several novel pulse sequences may be as good and possibly better for controlling the symptoms of Parkinson’s disease. Warren Grill at Duke, Peter Brown at Oxford and several other colleagues have been running similar studies, and it is likely we will soon see different stimulation settings for patients.  The beauty of this approach is that we can potentially re-program the battery just like we would update an app on a cellular phone.  This type of innovation will not require repeat DBS surgery.

Once we were able to demonstrate that we could use a scheduled stimulation strategy, our group quickly moved to real time physiological monitoring of the brain’s signals in an effort to “close the loop.”  When we say close the loop, we are referring to a process where we perform real-time monitoring of brain waves and we program the device to automatically respond to specific patterns which have been associated with pathological symptoms.  We first accomplished this with tics, and now we are attempting to capture and improve freezing of gait in Parkinson’s disease.  Closed loop stimulation really translates to smart stimulation.  We associate an abnormal brain wave with an unwanted symptom such as freezing.  When the device detects the abnormal brain wave it deploys a volley of electricity to neutralize it.(9)  We have experimented using technology from Medtronic (PC+S) and Neuropace.  Peter Brown and many other groups around the globe are also now testing closed loop approaches.  Closed loop smart stimulation will likely be employed in clinical practice in the next 5-10 years and is already in use for the treatment of epilepsy.

Selected References:

  1. Barbe MT, Maarouf M, Alesch F, Timmermann L. Multiple source current steering--a novel deep brain stimulation concept for customized programming in a Parkinson's disease patient. Parkinsonism & related disorders 2014;20:471-3.
  2. Pollo C, Kaelin-Lang A, Oertel MF, et al. Directional deep brain stimulation: an intraoperative double-blind pilot study. Brain : a journal of neurology 2014;137:2015-26.
  3. Toader E, Decre MM, Martens HC. Steering deep brain stimulation fields using a high resolution electrode array. Conference proceedings :  Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual Conference 2010;2010:2061-4.
  4. Martens HC, Toader E, Decre MM, et al. Spatial steering of deep brain stimulation volumes using a novel lead design. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 2011;122:558-66.
  5. Gunduz A, Morita H, Rossi PJ, et al. Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline. The International journal of neuroscience 2014:1-31.
  6. de Hemptinne C, Swann NC, Ostrem JL, et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease. Nature neuroscience 2015;18:779-86.
  7. Okun MS, Foote KD, Wu SS, et al. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA neurology 2013;70:85-94.
  8. Maling N, Hashemiyoon R, Foote KD, Okun MS, Sanchez JC. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome. PloS one 2012;7:e44215.
  9. Almeida L, Martinez-Ramirez D, Rossi PJ, Peng Z, Gunduz A, Okun MS. Chasing tics in the human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for tourette syndrome. Journal of clinical neurology 2015;11:122-31.
Posted: 5/6/2015 7:07:28 AM 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. 

April 2015
What to tell Parkinson’s patients about diet and taking statin drugs

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

February 2015
Tips for Parkinson’s Disease Patients Switching from Sinemet or Madopar to Rytary (IPX066)

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
The Importance of a Monitoring Strategy When Prescribing Dopamine Agonists: Lessons from the National Parkinson Foundation Data

October 2014
Is Midlife Migraine Related to Late Life Parkinson’s Disease?

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
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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