What's Hot in PD? Leaps in Deep Brain Stimulation Technology

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. 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). 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). 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 (STN) (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. 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. 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

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.

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.

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.

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.

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.

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.

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.

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.

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.

 

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the 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 and 10 Breakthrough Therapies for Parkinson's Disease.

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