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

描述（由申请人提供）：由于脊髓损伤（SCI）患者无法咳出清澈的分泌物，呼吸系统并发症导致其发病率和死亡率显着增加。 因此，他们依赖护理人员的协助来应用手动抽吸、辅助咳嗽动作或其他气道管理方法。 这些方法很麻烦，通常不舒服并且需要经过培训的人员。 这些人由于呼气肌麻痹而缺乏有效的咳嗽机制。 由于大多数受试者损伤平面以下的脊髓是完整的，因此脊髓的运动神经元和周围神经肌肉装置保持功能。 因此，呼气肌适合功能性电刺激技术。 在对 16 名四肢瘫痪患者进行的单点初步研究中，我们最近表明，可以通过脊髓刺激 (SCS) 电激活呼气肌，以恢复有效的咳嗽，该方法涉及通过椎板切开术切口手术放置椎间盘电极。 我们证明，这种方法成功地实现了呼气肌肉激活的有效手段，正如产生大的气道正压和呼气气流速率所证明的那样。 重要的是，该技术有助于清除分泌物， 减少对护理人员支持的需求，降低呼吸道感染的发生率并提高生活质量。 虽然成功，但电极放置需要侵入性且昂贵的手术。 因此，许多人不愿意采用这种技术。 根据动物和人体研究的结果，我们假设可以使用导线来实现呼气肌的类似激活，导线可以通过针经皮插入，从而无需侵入性椎板切开术，并且可以在门诊进行。 后一种手术将显着缩短手术时间、减轻手术程度、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，这项事业的目的有两个。 首先，使用所提出的刺激的线电极治疗慢性 SCS 的安全性 范式将在 SCI 动物模型中进行评估。 假设安全性分析令人满意，则将在 16 名 SCI 受试者中评估导线 SCS 的功效，评估该方法激活呼气肌、恢复有效咳嗽机制并实现与分泌管理相关的显着临床益处的能力。 鉴于该孤儿群体的显着异质性，受试者将作为自己的对照来评估该技术的成功。 如果成功，导丝系统将提供一种恢复咳嗽的微创方法，并有可能显着改善生活质量。 最终，通过 SCS 恢复有效咳嗽有可能显着 改善 SCI 患者与呼吸系统并发症相关的发病率和死亡率。 这项研究还将提供该技术的多中心试验所需的数据，从而最终获得 FDA 的批准。

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.