Research Insights

Advances in functional neurosurgery for Parkinson’s disease.

Movement Disorders

Metman LV, Slavin KV. Advances in functional neurosurgery for Parkinson’s disease. Movement Disorders, 2015 Sep 15;30(11):1461-70. doi: 10.1002/mds.26338. Epub 2015 Aug 14

Introduction:  Approximately 50 years ago, levodopa was introduced to treat Parkinson’s disease (PD) and many thought that such medication would generally replace invasive surgical techniques.  Although medication continues to be the first line therapy for PD, surgical intervention has actually grown and improved quite a bit.  The purpose of this article was to discuss the advances of deep brain stimulation (DBS), lesioning techniques, and gene and cellular therapies over the past few years.  

DBS: 

Timing: Typically DBS has been performed in people with PD (PWP) after medication trials are no longer effective many years into their disease.  However, recent studies have been completed with PWP that have had shorter duration PD and it was found that surgical intervention was promising as they had improved motor control, improved quality of life, and comparable adverse side effects with resolution as compared to medication treatment alone.  As a result of these studies there is now a FDA approved, double blind, placebo controlled, phase III clinical trial underway to better evaluate early intervention with DBS for PWP.

Target: There are conflicting studies regarding which target of DBS, subthalamic nucleus (STN) or globus pallidus interna (GPi), has the best outcomes for PWP.  Consensus generally indicates that the target of DBS should be chosen on a case by case basis for each individual with PD to tailor treatment for their disease, situation, and symptoms.  There is also an additional target, the peduncolupontine nucleus (PPN) but there are fewer studies regarding this target with variable results.  

Surgical Techniques: Intraoperative MRI (iMRI) is a newer technique that obviates the need for PWP to be awake during DBS and typically improves surgical accuracy.  iMRI involves the surgical procedure taking place in the same room as the MRI scanner and the surgeon receiving real time pictures to guide DBS lead placement.  So far, this imaging advancement has similar successful outcomes to the typical stereotactic frame/awake patient methodology.  There is a similar procedure for CT scanning, intraoperative CT (iCT) that is more readily available but does not have as much outcome research.  Lastly, surgeons have been evaluating whether or not DBS surgery can be performed with the same accuracy levels using a frameless approach versus the stereotactic frame.  Results are still pending but PWP undergoing DBS may find it more comfortable not to use the stereotactic frame during surgery and may spend less time in the operating room.

Technical Development: There have been significant advancements in how the programmer can set the stimulation settings for the PWP.  Research has not been overwhelming regarding shaping and steering approaches for the majority of PWP but some have greatly benefitted in improved motor control and reduced adverse events.  Research has also been done on routine low frequency stimulation which has improved swallowing difficulties, freezing of gait, postural control, and gait in some patients but the general conclusion is that one size does not fit all when it comes to stimulator frequency or patterns of DBS.  Another area of interesting research regarding the technology of DBS lies in the open versus closed loop system designs.  Current DBS uses an open loop system which does not monitor the PWP in-vivo symptoms, neurotransmitter levels, or needs to determine stimulator settings.  A closed loop system would do all of those things and may significantly increase stimulator battery life.  Animal model research has been promising but the closed loop system is still under significant development.  

Lesioning:  Ultrasound can be used for incisionless thalamotomy, pallidotomy, and subthalamic nucleotomy.  MRI guided ablation procedures (MRI guided focused ultrasound; MRgFU)have shown efficacy in small numbers of patients and is attractive as it does not involve opening the skull but such studies need to have improved study design that can show safety, accuracy, any adverse events, and efficacy of such treatment.  Concern will also remain that ablation destroys tissue which may make DBS more attractive for treatment of PD.  

Gene and Cellular Therapy:  Gene and cellular therapy has mixed findings in a variety of different types of studies.  Continued research in the safety, efficacy, and type of gene and cellular therapy will be important to determine benefits to PWP.
   
Conclusion:  Surgical intervention has shown great promise and efficacious treatment for PWP.  It will continue to be refined along with the collaboratively used technology for treatment of PD.  Surgery may change dramatically when the cure for PD is found but until then the surgical treatments are a very efficacious option for PWP.

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