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）患者的重要发病率和死亡率，因为他们无法咳嗽和清除分泌物。因此，他们依赖于护理人员协助应用手动吸痰，辅助咳嗽操作或其他气道管理方法。这些方法很麻烦，通常不舒服，需要训练有素的人员。由于他们的呼气肌麻痹，这些人缺乏有效的咳嗽机制。由于大多数受试者损伤水平以下的脊髓是完整的，脊髓和周围神经肌肉装置的运动神经元保持功能。因此，功能电刺激技术适用于呼气肌。在一项针对16名四肢瘫痪患者的试点研究中，我们最近表明，通过脊髓刺激（SCS）电激活呼气肌可以恢复有效的咳嗽，这种方法包括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激活的有效手段，正如产生大气道正压和呼气气流速率所证明的那样。重要的是，这种技术有助于分泌物的清除，

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.