Use of Two DBS Electrodes to Treat Post-Traumatic Tremor

描述(由申请者提供)：本K23奖项建议的目的是研究中间腹肌(VIM)加口腹前部/腹后部(VOA/VOP)脑深部刺激(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症的震颤往往会明显致残，对药物治疗也难以奏效。损伤和脑深部刺激的结果好坏参半，有些令人失望。此前，我们报告了两个DBS电极(一个在VIM/VOP交界处，一个在VOA/VOP交界处)用于治疗单个患者的创伤后震颤有效，此后我们在四名患者中进行了一项更大规模的先导性研究。这项研究将检验两个电极对创伤后和MS震颤的治疗效果好于一个电极的假设。20名患者将被招募并随机分为两组(VIM组和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，一半患者将接受VIM DBS，另一半患者将接受VOAA/OP DBS(只有一个设备激活-患者和检查人员失明)。在这一盲性评估期之后，所有患者的两个电极都将被激活，并在6个月时在四种随机条件下进行测试：VIM DBS ON-VOAA/OP DBS OFF、VIM DBS OFF-VOAA/OP DBS ON、VIM DBS ON-VOAA/OP DBS ON和VIM DBS OFF-VOAA/OP DBS OFF。测试将在临床研究中心(CRC)进行，为期四天。本研究不仅旨在评价双电极DBS治疗创伤后震颤和MS震颤的效果，而且还研究每个单独电极的效果以及该疗法的潜在副作用。希望这项研究将导致更有效的治疗药物难治性创伤后和MS震颤，并导致未来的R01建议，旨在发展DBS技术的创新应用。整个提案经过精心设计，以支持首席研究员作为临床研究员的发展。

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.