NEUROMODULATION THERAPY FOR FECAL INCONTINENCE

描述（由申请人提供）：粪便失禁（FI）影响8- 15%的美国人口，主要是妇女和老年人，以及45%的疗养院居民。它严重损害生活质量，并造成重大的卫生保健负担。FI的特征是骨盆底的显著神经肌肉功能障碍，包括双侧腰肛门直肠和骶肛门直肠神经病变和感觉运动功能障碍。这种多因素的病因学表明，适应不良的神经可塑性变化的神经支配下胃肠道可能发挥重要作用的发病机制FI。FI治疗进展的一个关键障碍是缺乏对治疗如何影响FI核心病理生理机制的理解，以及缺乏基于机制的非侵入性治疗。我们的目标是通过开发调节外周和中枢神经元扰动的疗法来解决FI的问题，从而改善内脏控制和感觉运动功能障碍，并了解这些治疗的神经生物学基础。我们的中心假设是，一种新型的非侵入性治疗，包括联合经腰磁刺激（rTLMS）和经骶磁刺激（rTSMS），将显着改善FI通过增强外周和中枢神经兴奋性，并将提供一个多方面的治疗效果，通过增强肛门肌肉力量，改善大便知觉和改善直肠容量。我们的方法是基于我们的初步研究表明，重复经腰磁刺激（rTLMS）和经骶磁刺激（rTSMS）改善肛门直肠疼痛和神经病变，并诱导中枢神经可塑性的变化。我们的目标是：1）解决我们对外周和中枢神经肠轴以及传入和传出神经信号的扰动如何影响FI的知识中的重大空白; 2）开发一种新的治疗FI的重复磁刺激。 本发明的目的在于提供一种用于改善神经刺激的方法，并确定rTLMS和rTSMS的可行性、安全性和最佳频率设置; 3）确定这种神经调节疗法的机制基础; 4）确定改善的位点是否位于传入或传出信号传导中或两者中。我们的预期结果包括开发新的治疗FI的方法，这些方法是基于机械的，有效的，安全的，低成本的，侵入性小，风险低，对患者依从性的依赖性小。我们项目的影响包括一种新的FI非侵入性治疗方式，这种治疗方法的发展的科学基础和提高对FI的外周和中枢神经肠轴的理解。

DESCRIPTION (provided by applicant): Fecal Incontinence (FI) affects 8-15 % of the US population, predominantly women and elderly, and 45% of nursing home residents. It significantly impairs quality of life and poses a major health care burden. FI is characterized by significant neuromuscular dysfunction of the pelvic floor that includes bilateral lumbo-anorectal and sacro-anorectal neuropathy and sensori-motor dysfunction. This multifactorial etiology suggests that maladaptive neuroplastic changes in the neural innervation of lower gastrointestinal tract could play a significant role in the pathogenesis of FI. A critical barrier o progress in the treatment of FI is the lack of understanding of how treatments affect the core pathophysiological mechanisms of FI and the absence of mechanistically based non-invasive therapies. Our goal is to address the problem of FI by developing therapies that modulate peripheral and central neuronal perturbations and thereby improve visceromotor control and sensori-motor dysfunctions, and to understand the neurobiologic basis of these treatments. Our central hypothesis is that a novel non-invasive treatment, consisting of combined translumbar magnetic stimulation (rTLMS) and transsacral magnetic stimulation (rTSMS), will significantly improve FI by enhancing peripheral and central neural excitability and will provide a multidimensional therapeutic effect by enhancing anal muscle strength, improving stool perception and improving rectal capacity. Our approach is based on our preliminary studies which suggest that repetitive translumbar magnetic stimulation (rTLMS) and transsacral magnetic stimulation (rTSMS) improve anorectal pain and neuropathy and induce central neuroplastic changes. Our objectives are to 1) address the significant gap in our knowledge regarding the peripheral and central neuroenteric axis and how perturbations in the afferent and efferent neural signaling can affect FI; 2) develop a new treatment for FI with repetitive magnetic stimulation and determine the feasibility, safety and optimal frequency setting of rTLMS and rTSMS; 3) determine the mechanistic basis for this neuromodulation therapy; 4) identify if the locus for improvement lies in the afferent or efferent signaling or both. Our expected outcomes include development of new treatment approaches for FI which are mechanistically based, effective, safe, low cost, less invasive, low risk and less dependent on patient compliance. The impact of our project include a new non-invasive treatment modality for FI, a scientific basis for the development of this treatment and improved understanding of the peripheral and central neuroenteric axis in FI.