Neurophysiological mechanism in sacral neuromodulation in patients suffering from fecal incontinence

本提案的目的是使用生物仿生学装置 在SPARC OT2计划内开发，以更好地了解神经生理机制 参与了治疗严重大便失禁的骶神经调节。与之相关的机制 骶神经刺激(SNS)的疗效还不是很清楚。一项综合的肛门直肠研究评价 压力波形(直肠力、肛门括约肌松弛)、方位(肛门直肠角和耻骨直肠肌 松弛)和袋子几何形状(直肠感觉、肛门大小和排出速度) 这种新颖的生物仿生设备将为我们深入了解社交网络的机制提供极大的帮助。一项临床研究是 在这个阶段，由于生物仿生学的新可能性，需要理解和推进神经调节 该领域的技术。因此，具体的目的是：1)确定神经的疏散效果 美敦力SNS治疗成功的一组FI患者的刺激。里程碑： 评价开/关刺激对肛门括约肌、直肠各部分的即刻神经调节作用 2)阐明改变刺激参数对排便系统的影响。 了解对一组患者排便系统中各种成分的影响 植入间质刺激器。里程碑：比较刺激参数对神经调节作用的影响 排便系统中的上述部件；以及3)将数学建模工具应用于 在AIMS 1-2中获得的数据有助于更深入地了解排便系统中的机械应力。 里程碑：使用肛门直肠行为的数学模拟来预测模式和神经调节 SNS响应者的感觉-运动反应机制。我们的建议旨在转移当前对骶骨的研究 使用先进的电子模拟凳子多维检查生理变化的神经调节 (例如，压力、变形性、生物力学、矢量和地形变化)。网络的影响 我们的项目是测试生物仿生学的能力，以提供对SNS作用机制的新理解 从而促进SNS疗法的改进。这可以改善预测和治疗方式，并 降低与治疗肛门直肠疾病相关的医疗成本，这些疾病随着 人口老龄化。我们期望获得关于SNS神经调节疗效的新知识和数据。这个 建议的研究将为设计一项前瞻性的多中心随访研究提供基础，在该研究中 患者组将在植入SNS前后进行研究，以进一步确定和预测无应答者。 我们的工业合作伙伴美敦力对拟议的研究和 支持属于南太平洋区域合作伙伴关系概念的后续研究。研究的影响是更好地理解 治疗中神经输入与肛门直肠功能和自知力的剂量-反应关系 机械装置。这可能有助于优化现有的方法，并导致新的治疗方式。

The objective of the present proposal is to use the Fecobionics device developed within the SPARC OT2 program to obtain better understanding of the neurophysiological mechanism involved in sacral neuromodulation for treatment of severe fecal incontinence. The mechanism related to efficacy of sacral nerve stimulation (SNS) is not well understood. An integrated anorectal study evaluating pressure waveforms (rectal force, anal sphincter relaxation), orientation (anorectal angle and puborectalis relaxation) and bag geometry (rectal sensation, anal dimensions, and expulsion velocity) during evacuation of the novel Fecobionics device would provide tremendous insight into the mechanism of SNS. A clinical study is needed at this stage, due to the new possibilities with Fecobionics, to understand and advance neuromodulatory technologies in the field. Accordingly, the Specific aims are 1) To determine the evacuatory efficacy of nerve stimulation in a group of patients with FI with successful treatment with the Medtronic Interstim SNS. Milestone: To evaluate the immediate neuromodulatory effect of on/off stimulation on components (anal sphincter, rectal sensitivity, puborectalis) in the defecatory system; 2) To elucidate the effect of altered stimulation parameters to obtain knowledge of influence on various components in the defecatory system in a group of patients with implanted Interstim stimulator. Milestone: To compare stimulation parameters on the neuromodulatory effect on abovementioned components in the defecatory system; and 3) To apply a mathematical modeling tool to the data obtained in Aims 1-2 to provide deeper understanding of mechanical stresses in the defecatory system. Milestone: To use mathematical simulation of anorectal behavior to predict patterns and neuromodulatory mechanisms of sensory-motor action in SNS responders. Our proposal seeks to shift current research in sacral neuromodulation by using an advanced electronic simulated stool for examining the physiologic changes, multidimensionally (e.g., pressure, deformability, biomechanics, vectoral and topographic changes). The impact of our project is to test Fecobionics capabilities to provide new understanding of SNS mechanisms of action and thereby facilitate improvements in SNS therapies. This can improve predictive and therapeutic modalities and reduce healthcare costs associated with treatment of anorectal disorders that are growing epidemic with the aging population. We expect to gain new knowledge and data on the efficacy of SNS neuromodulation. The proposed studies will provide the basis for designing a prospective multi-center follow-up study where a larger patient group will be studied before and after SNS implantation for further characterizing and prediction of non-responders. Our industrial partner Medtronic has expressed great interest in the proposed studies and for supporting follow-up studies falling within the SPARC concept. The impact of the study is a better understanding of dose-response relationships between neural input and anorectal function and insight in therapeutic mechanisms. This may help optimization of existing approaches and lead to new treatment modalities.