Evaluation of Spinal Cord Stimulation Using Wire Leads to Restore an Effective Co

描述(申请人提供)：在脊髓损伤(SCI)患者中，由于不能咳嗽和分泌物清澈，呼吸系统并发症是导致严重发病率和死亡率的主要原因。因此，他们依赖于护理者的帮助来应用手动吸痰、辅助咳嗽或其他呼吸道管理方法。这些方法很麻烦，通常不舒服，而且需要训练有素的人员。这些人缺乏有效的咳嗽机制，因为他们的呼气肌瘫痪。由于损伤平面以下的脊髓在大多数受试者中是完整的，脊髓的运动神经元和周围神经肌肉机构仍有功能。因此，呼气肌对功能性电刺激技术是适用的。在对16名四肢瘫痪患者进行的一项单一部位的初步研究中，我们最近表明，脊髓刺激(SCS)可以电激活呼气肌，以恢复有效的咳嗽，这是一种通过椎板切开手术放置椎间盘电极的方法。我们证明了这种方法在实现呼气肌肉激活方面是成功的，正如产生大的正呼吸道压力和呼气气流速率所证明的那样。重要的是，这项技术有助于分泌物的去除， 减少对照顾者支持的需求，减少呼吸道感染的发生率，提高生活质量。虽然成功，但电极放置需要一种侵入性和昂贵的程序。因此，许多人不愿追求这项技术。基于动物和人体研究的结果，我们的假设是，呼气肌可以通过针经皮插入钢丝导线实现类似的激活，从而消除了侵入性椎板切开术的需要，并且可以在门诊进行。后一种方法将显著缩短手术时间，减少手术程度，缩短恢复时间，降低成本，从而提高患者和医生对该技术的接受度。因此，这项承诺的目的有两个。首先，利用所提出的刺激方案，采用线电极治疗慢性SCS的安全性 范式将在脊髓损伤的动物模型中进行评估。假设安全性分析结果令人满意，接下来将评估16例脊髓损伤患者使用钢丝导联的SCS的有效性，即这种方法激活呼气肌的能力，恢复有效的咳嗽机制，并获得与分泌物管理相关的显著临床益处。鉴于这一孤儿群体的显著异质性，受试者将作为自己的对照来评估这项技术的成功。如果成功，导线系统将提供一种微创的止咳方法，并有可能显著提高生活质量。最终，SCS有效咳嗽的恢复有可能显著 改善脊髓损伤患者与呼吸道并发症相关的发病率和死亡率。这项研究还将为最终获得FDA批准的这项技术的多中心试验提供必要的数据。

DESCRIPTION (provided by applicant): Respiratory complications account for significant morbidity and mortality in persons with spinal cord injury (SCI) due to their inability to cough an clear secretions. Consequently, they are dependent upon caregiver assistance for the application of manual suctioning, assisted coughing maneuvers or other methods of airway management. These methods are cumbersome, generally uncomfortable and require trained personnel. These individuals lack an effective cough mechanism due to paralysis of their expiratory muscles. Since the spinal cord below the level of injury is intact in most subjects, th motoneurons of the spinal cord and peripheral neuromuscular apparatus remain functional. Therefore, the expiratory muscles are amenable to functional electrical stimulation techniques. In a single site, pilot study of 16 tetraplegics, we have recently shown that the expiratory muscles can be electrically activated by spinal cord stimulation (SCS) to restore an effective cough, a method which involves the surgical placement of disc electrodes through laminotomy incisions. We demonstrated that this method is successful in achieving an effective means of expiratory muscle activation, as demonstrated by the generation of large positive airway pressures and expiratory airflow rates. Importantly, this technique facilitates secretion removal, reduces the need for caregiver support, reduces the incidence of respiratory tract infections and improves life quality. While successful, electrode placement requires an invasive and costly procedure. Consequently, many individuals were unwilling to pursue this technique. Based upon the results of animal and human studies, it is our hypothesis that comparable activation of the expiratory muscles can be achieved with wire leads which can be inserted percutaneously through a needle, eliminating the need for the invasive laminotomy procedure and can be performed on an out-patient basis. This latter procedure would significantly shorten surgical time, lessen the degree of surgery, shorten recovery time, reduce costs, and thereby, increase patient and physician acceptance of this technique. The purpose of this undertaking, therefore, is two-fold. First, the safety of chronic SCS with wire electrodes utilizing the proposed stimulus paradigm will be assessed in an animal model of SCI. Assuming a satisfactory safety analysis, the efficacy of SCS with wire leads will then be assessed in 16 subjects with SCI, in terms of the capacity of this method to activate the expiratory muscles, restore an effective cough mechanism and achieve significant clinical benefits related to secretion management. Given the significant heterogeneity of this orphan population, subjects will serve as their own controls to evaluate the success of this technique. If successful, the wire lead system will provide a minimally invasive method of restoring cough, and has the potential to significantly improve life quality. Ultimately, restoration of an effective cough with SCS has the potential to significantly improve the morbidity and mortality associated with respiratory complications in persons with SCI. This study will also provide the data necessary for a multi-center trial of this technique leading to eventual FDA approval.