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

描述（由申请人提供）：呼吸系统并发症是脊髓损伤（SCI）患者的主要发病率和死亡率，因为他们无法咳嗽出清晰的分泌物。 因此，它们依赖于护理人员的帮助来应用手动抽吸、辅助咳嗽操作或其他气道管理方法。 这些方法麻烦，通常不舒服，并且需要受过训练的人员。 这些人由于呼气肌麻痹而缺乏有效的咳嗽机制。 由于在大多数受试者中，损伤水平以下的脊髓是完整的，因此脊髓的运动神经元和外周神经肌肉装置保持功能。 因此，呼气肌适合于功能性电刺激技术。 在一个单一的网站，试点研究16四肢瘫痪，我们最近表明，呼气肌可以电激活脊髓刺激（SCS），以恢复有效的咳嗽，一种方法，其中涉及通过椎板切开术切口的手术放置圆盘电极。 我们证明，这种方法是成功地实现呼气肌激活的有效手段，如通过产生大的气道正压和呼气气流速率所证明的。 重要的是，这种技术有助于分泌物的去除， 减少了对护理人员支持的需求，降低了呼吸道感染的发病率，提高了生活质量。 虽然成功，但电极放置需要侵入性和昂贵的程序。 因此，许多人不愿意追求这种技术。 基于动物和人体研究的结果，我们假设，呼气肌的类似激活可以用导线实现，导线可以通过针经皮插入，消除了对侵入性椎板切开术程序的需要，并且可以在门诊患者的基础上进行。 后一种方法将显著缩短手术时间，减轻手术程度，缩短恢复时间，降低成本，从而增加患者和医生对该技术的接受度。 因此，这项工作有两个目的。 首先，使用所提出的刺激的线电极的慢性SCS的安全性 将在SCI的动物模型中评估范例。 假设安全性分析令人满意，则将在16例SCI受试者中评估带导线的SCS的疗效，评估该方法激活呼气肌、恢复有效咳嗽机制并实现分泌物管理相关的显著临床获益的能力。 鉴于该孤儿人群的显著异质性，受试者将作为其自身对照，以评价该技术的成功。 如果成功，导线系统将提供一种微创的方法来恢复咳嗽，并有可能显着改善生活质量。 最终，SCS恢复有效咳嗽有可能显著改善患者的咳嗽症状。 改善SCI患者呼吸系统并发症相关的发病率和死亡率。 这项研究还将为这项技术的多中心试验提供必要的数据，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.