Use of Two DBS Electrodes to Treat Post-Traumatic Tremor

描述（由申请人提供）：本K23奖提案的目的是研究中间腹肌（Vim）+口腹前肌/口腹后肌（VOA/VOP）脑深部电刺激（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MS震颤往往是显着致残和难治性的药物治疗。损伤和深部脑刺激的结果好坏参半，有些令人失望。之前，我们报告了使用两个DBS电极（一个在Vim/VOP边界，一个在VOA/VOP边界）对单个患者的创伤后震颤治疗有效，并且此后在4名患者中进行了更大规模的初步研究。本研究将检验两个电极治疗创伤后和MS震颤优于一个电极的假设。将招募20例患者并随机分为两组（Vim与VOAA/OP）。所有患者将植入两个电极，但是，在研究的前3个月，一半患者将植入Vim DBS，一半患者植入VOAA/OP DBS（仅激活一个器械-患者和检查者均设盲）。在该盲态评价期后，所有患者都将激活两个电极，并在6个月时在4种随机条件下进行测试：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打开和Vim DBS关闭- VOAA/OP DBS关闭。测试将在临床研究中心（CRC）进行四天。该研究的目的不仅是评估双电极DBS治疗创伤后和MS震颤的效果，而且还研究了每个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R 01建议，旨在开发DBS技术的创新应用。总体方案经过精心设计，以支持主要研究者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.