Phase-Specific DBS Suppresses Postural and Kinetic Tremor

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

• Phase-specific deep brain stimulation (DBS) can provide relief for patients with essential tremor (ET) during different motor states, including both kinetic (during continuous movement) and postural (during isometric contraction) tremor.

• Phase-specific DBS may be better suited for patients with stable tremor and for whom the side effects of conventional DBS are a concern.

Why This Matters

• ET affects up to 6.3% of adults aged 65 years or older.

• DBS is used to regulate abnormal brain synchrony in patients with ET, but on-demand DBS that triggers stimulation only when a specific marker is sensed could decrease stimulation-induced side effects and increase the neurostimulator’s battery life.

• Because patterns of thalamic neural activity reflect the pattern of limb movement during an episode of postural tremor, the patient’s tremor episodes can be used to determine the best stimulation strategy.

• A trial of phase-specific, closed-loop DBS controlled by limb acceleration was reported by Cagnan and colleagues in 2017. The current study, designed to build on this work by testing the effects during both kinetic tremor and postural tremor and to further explore the relationship between central and peripheral tremor, corroborates the findings of Cagnan and colleagues.

Study Design

• The primary objective was to investigate the efficacy of phase-specific DBS in different contexts and motor states.

• Four patients with upper-limb ET and implanted DBS electrodes participated in the study.

• The index finger of the patient’s most tremulous hand was fitted with a triaxial accelerometer. The signals were amplified and recorded during four different stimulation paradigms while the patient folded the forearms inward, with hands pointing toward each other at nose level, and also while drawing inward and outward spirals on a digitizing tablet.

• The four stimulation paradigms tested were no stimulation, random-search stimulation, phase-specific stimulation, and conventional high-frequency stimulation.

• During random-search stimulation and phase-specific stimulation, an investigational device, the Nexus-D2 (Medtronic), was used to close the stimulation loop.

Key Results

• Phase-specific DBS resulted in significant postural tremor suppression in three of the four patients.

• It also showed significant kinetic tremor suppression in two of three patients.

• However, high-frequency stimulation was more effective than phase-specific stimulation in both motor states.

• Phase-specific DBS may be most appropriate when patients have stable tremor characteristics and when the side effects of high-frequency DBS are a limiting factor.

Limitations

• The study included only four patients; the results should be validated in a larger cohort.

• The patients’ DBS electrodes targeted either the ventral intermediate thalamus (one patient) or the posterior subthalamic area. Because of the small sample size, the authors did not compare the stimulation effects according to the two targets.

Disclosures

• The study was supported by the National Institute for Health Research Oxford Biomedical Research Centre and the Medical Research Council (United Kingdom).

• The Nexus-D2 investigational device was provided by Medtronic.

• One author was an employee of Medtronic when the study was initiated, and another author has consulted for Medtronic.

This is a summary of a preprint research study , “Phase-Specific Deep Brain Stimulation Revisited: Effects of Stimulation on Postural and Kinetic Tremor ,” written by Carolina Reis, from the University of Oxford, United Kingdom, and colleagues. This study was published on medRxiv.org and is provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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