Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor

Alexia-Sabine Moldovan; Christian Johannes Hartmann; Carlos Trenado; Nicola Meumertzheim; Philipp Jörg Slotty; Jan Vesper; Alfons Schnitzler; Stefan Jun Groiss

doi:10.1016/j.brs.2018.04.019

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor

Brain Stimul. 2018 Sep-Oct;11(5):1132-1139. doi: 10.1016/j.brs.2018.04.019. Epub 2018 Apr 26.

Authors

Alexia-Sabine Moldovan¹, Christian Johannes Hartmann¹, Carlos Trenado², Nicola Meumertzheim¹, Philipp Jörg Slotty³, Jan Vesper³, Alfons Schnitzler¹, Stefan Jun Groiss⁴

Affiliations

¹ Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
² Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Psychology and Neurosciences, Translational Neuromodulation Unit, Leibniz Centre for Working Environment and Human Factors, TU Dortmund, Dortmund, Germany.
³ Department of Functional and Stereotactic Neurosurgery, Center for Neuromodulation, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
⁴ Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. Electronic address: groiss-js@umin.net.

PMID: 29735344
DOI: 10.1016/j.brs.2018.04.019

Abstract

Background: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET).

Objective: To compare the DBS effect of shorter pulse width at 40 μs (DBS-40 μs) to conventional pulse width at 60 μs (DBS-60 μs) on the therapeutic window in ET patients.

Methods: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 μs and DBS-60 μs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width.

Results: DBS-40 μs showed a significantly larger therapeutic window than DBS-60 μs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 μs and DBS-60 μs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 μs compared to DBS-60 μs.

Conclusions: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window.

Keywords: Deep brain stimulation; Essential tremor; PSA; Pulse width; Therapeutic window; VIM.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Deep Brain Stimulation / adverse effects
Deep Brain Stimulation / methods*
Double-Blind Method
Essential Tremor / therapy*
Female
Humans
Male
Middle Aged
Subthalamus / physiopathology