Use of Two DBS Electrodes to Treat Post-Traumatic Tremor

描述（由申请人提供）：这项K23奖提案的目的是研究正中腹肌（VIM）加前口腹肌/后口腹肌（VOA/VOP）深部脑刺激（DBS）治疗创伤后和多发性硬化症（MS）震颤的安全性和有效性。创伤后和多发性硬化震颤往往是显着致残和难以药物治疗。损伤和深部脑刺激的结果好坏参半，有些令人失望。先前，我们报道了使用两个DBS电极（一个在VIM/VOP边界，一个在VOA/VOP边界）有效治疗单个患者的创伤后震颤，并对该病例进行了更大的试点研究。这项研究将验证两个电极比一个电极更好地治疗创伤后和多发性震颤的假设。将招募20名患者并随机分为两组（VIM组与VOAA/OP组）。所有患者都将植入两个电极，然而，在研究的前3个月，一半的患者将使用VIM DBS，一半的患者将使用VOAA/OP DBS（只有一个设备被激活-患者和检查者盲法）。在盲法评估期之后，所有患者的两个电极都将被激活，6个月后将在四种随机情况下进行测试：VIM DBS打开- VOAA/OP DBS关闭，VIM DBS关闭- VOAA/OP DBS打开，VIM DBS打开- VOAA/OP DBS打开，VIM DBS打开- VOAA/OP DBS关闭，VIM DBS关闭- VOAA/OP DBS关闭。测试将在临床研究中心（CRC）进行四天。本研究不仅旨在评估双电极DBS治疗创伤后和多发性震颤的效果，而且还研究了每个电极的效果，以及这种治疗的潜在副作用。希望本研究能够更有效地治疗药物难治性创伤后和多发性震颤，并为DBS技术创新应用的发展提供未来的R01建议。整个提案经过精心设计，以支持首席研究员作为临床研究者的发展。

DESCRIPTION (provided by applicant): The objective of this K23 Award proposal is to investigate the safety and efficacy of ventralis intermedius (VIM) plus ventralis oralis anterior/ventralis oralis posterior (VOA/VOP) deep brain stimulation (DBS) for the treatment of post-traumatic and multiple sclerosis (MS) tremor. Post-traumatic and MS tremors tend to be markedly disabling and refractory to medical therapy. Lesions and deep brain stimulation have had mixed and somewhat disappointing results. Previously, we reported the use of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border) as effective for the treatment of post-traumatic tremor in a single patient, and have since followed up this case with a larger pilot study in four patients. This study will test the hypothesis that two electrodes are better than one for treatment of post-traumatic and MS tremor. Twenty patients will be recruited and randomized into two groups (VIM versus VOAA/OP). All patients will have two electrodes implanted, however, for the first 3 months of the study half of the patients will have VIM DBS, and half VOAA/OP DBS (only one device activated - patient and examiner blinded). Following this blinded period of evaluation, all patients will have both electrodes activated, and at 6 months will be tested in four randomized conditions: VIM DBS on - VOAA/OP DBS off, VIM DBS off - VOAA/OP DBS on, VIM DBS on - VOAA/OP DBS on, and VIM DBS off - VOAA/OP DBS off. Testing will be performed in the clinical research center (CRC) over four days. The study aims not only to evaluate the effects of dual electrode DBS for the treatment of post-traumatic and MS tremor, but also to investigate the effects of each individual electrode, as well as potential side effects of this therapy. It is hoped that this study will result in more effective treatment of medication refractory post-traumatic and MS tremor, and lead to future R01 proposals aimed at the development of innovative applications of DBS technology. The overall proposal has been carefully designed to support the principal investigator's development as a clinical investigator.