1 Department of Neurosurgery, Bern University Hospital, Inselspital, Bern, Switzerland
2 Department of Neurology, Bern University Hospital, Inselspital, Bern, Switzerland.
Brain. 2014 Jul;137(Pt 7):2015-26. doi: 10.1093/brain/awu102. Epub 2014 May 19.
Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.
不同靶点的深部脑刺激已被证明可以极大地改善多种神经疾病的症状。然而，致残副作用的发生可能会限制达到最大益处所需的足够电流的输送能力。计算模型表明，减小电极尺寸和提供定向刺激的能力可以提高此类治疗的疗效。但这在人类中从未得到过证实。在本研究中，我们评估了与全方位刺激相比，定向刺激的效果。在 11 例帕金森病患者的丘脑底核和另外 2 例原发性震颤患者的丘脑腹中间核中，在手术过程中测试了三种不同的刺激方向以及全方位刺激。在为植入最终电极选择的轨迹上，我们评估了正性和副作用之间的电流阈值窗口，即治疗窗口。使用计算有限元模型比较了当刺激一个定向电极或进行全方位刺激时，激活的组织体积。除 1 例患者外，所有患者均显示定向刺激优于全方位刺激。所有患者均观察到最佳刺激方向。最佳方向的治疗窗口比第二佳方向宽（P = 0.003），比第三佳方向宽（P = 0.002）。与全方位方向相比，最佳方向的治疗窗口宽 41.3%（P = 0.037）。在最佳方向产生有意义的治疗效果的电流阈值为 0.67 mA（0.3-1.0 mA），比全方位刺激低 43%（P = 0.002）。由于插入定向电极或测试过程中未发生任何并发症。计算模型显示，在全方位模式下，激活的组织体积为 10.5 mm(3)，而仅使用一个电极时为 4.2 mm(3)。与全方位刺激相比，在丘脑底核和丘脑腹中间核中，手术时应用减小的电极尺寸进行定向深部脑刺激显著扩大了治疗窗口，并降低了产生有益效果所需的电流。与刺激方向相关的观察到的副作用与周围结构的解剖位置一致。这种新方法为改善深部脑刺激治疗开辟了道路。进一步需要进行慢性植入以证实这些发现。
