Novel targets and stimulation paradigms for deep brain stimulation

Abstract

Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

Keywords:

• deep brain stimulation
• movement disorders
• neuromodulation
• neurostimulation
• Parkinson disease

Financial & competing interests disclosure

Dr. Hess has served as a speaker for the National Parkinson Foundation and the Davis Phinney Foundation has participated in CME and educational activities on movement disorders sponsored by Allergan, Ipsen and Mertz Pharmaceuticals. Dr. Okun serves as a consultant for the National Parkinson Foundation, and has received research grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association and the UF Foundation. Dr. Okun has previously received honoraria, but has received no support from industry in the past 60 months. Dr. Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books). Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. Dr. Okun has lectured in CME activities for PeerView, Prime, Quantia, Henry Stewart, and by Vanderbilt University. Dr. Okun receives grants from Medtronic, Abbvie, and ANS/St. Jude, and the PI has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Deep brain stimulation (DBS) is approved by the US FDA for Parkinson disease (PD), essential tremor (ET), dystonia and severe treatment-resistant obsessive–compulsive disorder (OCD) in the USA and for refractory epilepsy in Canada, Europe and Australia. Established targets for DBS include subthalamic nucleus and globus pallidus internus in PD, ventral intermediate nucleus in essential tremor, globus pallidus internus for dystonia and anterior limb of internal capsule for OCD.

• It is unlikely that the typical DBS targets used for PD will provide significant benefit in atypical parkinsonism, although novel targets being investigated may be potential targets in the future.

• Recent advances in stimulation paradigms and hardware include constant current and interleaving stimulation, current steering, and closed-loop or adaptive DBS. These advances may improve efficacy, reduce side effects and energy consumption, and help to uncover the underlying therapeutic mechanisms of DBS.

• Novel targets are being investigated in PD and may be potential adjunctive targets for motor symptoms not fully responsive to traditional targets.

• DBS therapy is being explored as a treatment option in new diseases, including Tourette’s syndrome, psychiatric diseases and Alzheimer’s disease.

Notes