Deep brain stimulation in essential tremor: targets, technology, and a comprehensive review of clinical outcomes

ABSTRACT

Introduction: Essential tremor (ET) is a common movement disorder with an estimated prevalence of 0.9% worldwide. Deep brain stimulation (DBS) is an established therapy for medication refractory and debilitating tremor. With the arrival of next generation technology, the implementation and delivery of DBS has been rapidly evolving. This review will highlight the current applications and constraints for DBS in ET.

Areas covered: The mechanism of action, targets for neuromodulation, next generation guidance techniques, symptom-specific applications, and long-term efficacy will be reviewed.

Expert opinion: The posterior subthalamic area and zona incerta are alternative targets to thalamic DBS in ET. However, they may be associated with additional stimulation-induced side effects. Novel stimulation paradigms and segmented electrodes provide innovative approaches to DBS programming and stimulation-induced side effects.

KEYWORDS:

• Constant current
• current steering
• deep brain stimulation
• segmented leads
• essential tremor
• posterior subthalamic area
• ventralis intermedius nucleus
• zona incerta

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Article Highlights

• The posterior subthalamic area and zona incerta are novel, effective targets for ET DBS, but may be associated with more stimulation-induced ataxia

• Connectivity profiling, constant current stimulation, and segmented DBS electrodes are emerging features that will assist in DBS optimization

• Unilateral VIM DBS provides substantial contralateral and modest ipsilateral tremor suppression, and has been shown in select cases to be sufficient for management of axial tremors in ET

• Dysarthria, ataxia, and gait instability are common adverse effects of ET DBS that are more frequent after bilateral than unilateral procedures, and may result from both microthalamotomy effects and from stimulation-induced side effects

• Loss of long-term efficacy in ET DBS is not uncommon and is due primarily to disease progression rather than to tolerance and/or habituation.

Declaration of Interest

JK Wong’s research is supported by NIH 1R25NS108939-01. CW Hess has served as a site investigator or co-investigator for research projects funded by the Parkinson’s Foundation and has served as a research committee member for the Michael J. Fox Foundation. CW Hess has served as a speaker for the National Parkinson Foundation, the Parkinson’s Disease Foundation, and the Davis Phinney Foundation. CW Hess has participated in CME and educational activities on movement disorders sponsored by Allergan, Ipsen, Mertz Pharmaceuticals, Peerview Online, UptoDate, and QuantiaMD. EH Middlebrooks has received research support from Varian Medical Systems, Inc. and Boston Scientific. L Almeida serves as consultant and has received honoraria from Medtronic and Boston Scientific. MS Okun serves as a consultant for the Parkinson’s Foundation, and has received research grants from NIH, Parkinson’s Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MS Okun ’s DBS research is supported by: R01 NR014852 and R01NS096008. MS Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford, and Cambridge (movement disorders books). MS Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. MS Okun has participated in CME and educational activities on movement disorders sponsored by the Academy for Healthcare Learning, PeerView, Prime, QuantiaMD, WebMD/Medscape, Medicus, MedNet, Einstein, MedNet, Henry Stewart, American Academy of Neurology, Movement Disorders Society and by Vanderbilt University. The institution and not MS Okun receives grants from Medtronic, Abbvie, Abbott, and Allergan and the primary investigator has no financial interest in these grants. MS Okun has participated as a site primary investigator and/or co-I for several NIH, foundation, and industry-sponsored trials over the years but has not received honoraria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was financially supported in part by National Institutes of Health grant: [NIH 1R25NS108939-01].