Date Published: June 19, 2019
Publisher: Public Library of Science
Author(s): T. A. Khoa Nguyen, Milan Djilas, Andreas Nowacki, André Mercanzini, Michael Schüpbach, Philipp Renaud, Claudio Pollo, Mathias Toft.
Segmented deep brain stimulation leads in the subthalamic nucleus have shown to increase therapeutic window using directional stimulation. However, it is not fully understood how these segmented leads with reduced electrode size modify the volume of tissue activated (VTA) and how this in turn relates with clinically observed therapeutic and side effect currents. Here, we investigated the differences between directional and omnidirectional stimulation and associated VTAs with patient-specific therapeutic and side effect currents for the two stimulation modes.
Nine patients with Parkinson’s disease underwent DBS implantation in the subthalamic nucleus. Therapeutic and side effect currents were identified intraoperatively with a segmented lead using directional and omnidirectional stimulation (these current thresholds were assessed in a blinded fashion). The electric field around the lead was simulated with a finite-element model for a range of stimulation currents for both stimulation modes. VTAs were estimated from the electric field by numerical differentiation and thresholding. Then for each patient, the VTAs for given therapeutic and side effect currents were projected onto the patient-specific subthalamic nucleus and lead position.
Stimulation with segmented leads with reduced electrode size was associated with a significant reduction of VTA and a significant increase of radial distance in the best direction of stimulation. While beneficial effects were associated with activation volumes confined within the anatomical boundaries of the subthalamic nucleus at therapeutic currents, side effects were associated with activation volumes spreading beyond the nucleus’ boundaries.
The clinical benefits of segmented leads are likely to be obtained by a VTA confined within the subthalamic nucleus and a larger radial distance in the best stimulation direction, while steering the VTA away from unwanted fiber tracts outside the nucleus. Applying the same concepts at a larger scale and in chronically implanted patients may help to predict the best stimulation area.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has demonstrated efficacy in treating motor symptoms of Parkinson’s disease [1,2]. It delivers electrical pulses at high stimulation frequencies to pathogenic brain areas using leads with four (Medtronic Activa, Abbott St Jude Libra) to eight (Boston Scientific Vercise) ring electrodes. Most implanted DBS systems provide current delivery in all directions around the electrode. This omnidirectional mode has shown to significantly improve motor symptoms, but unintended stimulation of surrounding anatomical structures can induce disabling side effects such as tonic muscular contraction, dysarthria, conjugate eye deviation, paresthesia, or gait imbalance [3–5]. More specifically, unintended stimulation of the non-motor parts of the STN may cause behavioral impairments and limbic side effects such as depression and impulsivity [6–8]. To reduce or avoid these side effects, one can decrease the stimulation amplitude. However, this typically reduces treatment efficacy as less stimulation is directed towards the target structure, which is the dorsolateral, or motor part, of the STN .
Nine patients were tested intraoperatively with a segmented lead. From the three directional electrodes tested, only the best directional electrode was considered for further analysis to better understand the potential benefits of directional stimulation. This best directional electrode was determined by the largest therapeutic window, i.e., the difference between side effect and therapeutic currents (note that all directional electrodes yielded full effect on rigidity). Therapeutic and side effect currents for directional and omnidirectional stimulation are listed in Table 1.
The present study investigated changes in VTA with segmented DBS leads that have smaller sized, but directional electrodes. These changes were related to intraoperative clinical testing in Parkinson’s disease patients that received DBS in the subthalamic nucleus.
Deep brain stimulation of the STN performed with segmented leads and reduced electrode size resulted in a decreased VTA and increased radial distance at therapeutic currents. Moreover, VTAs were consistently confined inside the anatomical boundaries of the STN at therapeutic currents, whereas they predominantly spread beyond the STN at side effect currents in the direction of undesired fiber tracts. The clinical benefits of directional stimulation are likely to be obtained through a VTA confined within the STN, while steering VTA away from unwanted fiber tracts outside the nucleus. Applying the same concepts at a larger scale and in chronically implanted patients may help to predict the best stimulation area according to specific symptoms using segmented leads.