Short pulse width widens the therapeutic window of subthalamic neurostimulation

Abstract

We explored the impact of pulse durations <60 μsec on the therapeutic window of subthalamic neurostimulation in Parkinson's disease. Current thresholds for full rigidity control and first muscle contractions were evaluated at pulse durations between 20 and 120 μsec during a monopolar review session in four patients. The average therapeutic window was 2.16 mA at 60 μsec, which proportionally increased by 182% at 30 μsec, while decreasing by 46% at 120 μsec. Measured chronaxies and model data suggest, that pulse durations <60 μsec lead to a focusing of the neurostimulation effect on smaller diameter axons close to the electrode while avoiding stimulation of distant pyramidal tract fibers.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

“…5). As previously suggested, a shorter pulse duration of 560 ms could constitute an alternative approach of selectively stimulating dentato-thalamic fibres close to the DBS lead based on divergent chronaxies of different subthalamic fibre tracts (Reich et al, 2015).…”

“…However, it was recently shown that VTA mirrored such neuronal proprieties as clinically defined (i.e. chronaxies) (Reich et al, 2015). Finally, VTA assumes that the primary effect of DBS is to activate myelinated axons, which was proved by several studies (Holsheimer et al, 2000;Paxinos and Mai, 2004;Groppa et al, 2014).…”

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s disease

“…While the authors were not able to stimulate at pulse widths shorter than 60 µs, they were able to conclude that a stimulation pulse width closer to the chronaxie of tremor suppression would provide a wider therapeutic window between tremor relief and induction of side effects such as ataxia (15). Following this, Reich et al used model derived strength-duration curves for STN stimulation in PD patients to demonstrate a widening difference in the action potential initiation thresholds between small diameter fibres close to the electrode and larger diameter fibres further away, thought to correspond to therapeutic effects and adverse effects respectively (14).…”

“…They also noted that despite using a higher stimulation current at lower PWs, the energy used in terms of charge per pulse was actually lower than at 60µs. However, efficacy thresholds could not be determined in many patients at PWs below 30µs due to the need for very high stimulation current (14).…”

“…Moreover, there are suggestions from modelling data that various PWs may selectively stimulate different neural elements (14,15). A wider TW than currently exists may provide more scope to increase stimulation both initially and over time without the occurrence of adverse effects at the level required for optimal control of PD motor symptoms.…”