Safety & Efficacy of Nerve Rerouting to treat Neurogenic Bladder in Spina Bifida

描述（由申请人提供）：脊柱裂是一种先天性脊髓缺陷，会导致神经损伤以及腰部以下感觉和肌肉功能丧失，从而导致肠、膀胱和性功能障碍。患者不能排尿或经常尿湿，这种情况持续一生，导致主要的生活质量和健康问题。清洁间歇导尿通常需要正确排空膀胱。通常需要抗毒蕈碱药物来缓解可导致不可逆肾损伤的高尿路压力，透析或肾移植是维持生命的唯一途径。肖医生在中国开发并正在执行一种新的手术，将功能正常的腰脊神经根连接到控制膀胱的骶神经。最终的结果是产生一种新的反射，通过刮擦或刺激由脊神经根供应的皮肤，膀胱可以排空。他报告说，在92名SCI患者中，88%的患者在神经改道手术后一年内恢复了膀胱控制，在110名脊柱裂儿童中，一年内成功率为87%。然而，在中国，严格的随访是具有挑战性的，因此关于术后神经恢复，特别是第一年发生的并发症和结果，以及中枢神经系统重塑在实现成功结局中可能发挥的潜在作用，仍有很多未知数。在博蒙，一项针对9名脊柱裂受试者的试点研究正在进行中，但美国目前没有其他中心正在研究这项技术。我们的初步数据非常有希望，9例受试者术后12个月，7/9例受试者自愿或通过刺激新的反射机制排尿。本项目旨在扩大我们的试点经验，进行更大规模和更严格的研究，以确定拟议的躯体-自主神经反射通路手术在脊柱裂患者中获得膀胱和肠道控制的安全性和有效性。此外，我们将系统地评估和优化新的躯体-自主神经反射弧的激发频率和位置，以a）更深入地了解与神经改道相关的神经恢复，以及B）科学和系统地确定理想的刺激参数，以实现最佳排尿结果，并使躯体-自主神经反射通路改道对患者最有用。实现本提案中概述的目标将有助于牢固确立该手术的安全性和有效性，并彻底改变脊柱裂患者膀胱和肠功能障碍的治疗。公共卫生相关性：脊柱裂是一种先天性脊髓缺陷，会导致神经损伤，导致肠、膀胱和性功能障碍。肖博士在中国开发了一种新的手术方法来重新连接影响膀胱的神经，该项目旨在科学地确定手术的安全性和有效性。

DESCRIPTION (provided by applicant): Spina Bifida, a congenital defect of the spinal cord, causes nerve damage and a loss of sensation and muscle function below the waist resulting in bowel, bladder and sexual dysfunction. Patients cannot urinate or are constantly wet, and this continues throughout life causing major quality of life and health problems. Clean intermittent catheterization is usually needed to empty the bladder properly. Antimuscarinic medications are commonly required to alleviate high urinary tract pressures that can cause irreversible kidney damage, where dialysis or kidney transplant is the only way to sustain life. Dr. Xiao developed and is performing a novel procedure in China that connects a functioning, healthy lumbar spinal nerve root to the sacral nerve that controls the bladder. The end result is the creation of a new reflex where the bladder can be emptied by scratching or stimulating the skin supplied by that spinal nerve root. He has reported that in 92 SCI patients, 88% regained bladder control within one year after the nerve rerouting surgery and in 110 children with spina bifida, reported success in 87% at one year. However, in China rigorous follow up is challenging, therefore much is still unknown about the neurorecovery post surgery, complications and results occurring in the first year in particular, and the potential role that central nervous system remodeling may play in achieving successful outcomes. At Beaumont, a pilot study is underway on 9 spina bifida subjects, however no other center in the US is currently studying this technique. Our preliminary data are very promising, and with 9 subjects now 12 months post procedure, 7/9 subjects are voiding either voluntarily or by stimulating the new reflex mechanism. This project aims to expand upon our pilot experience to conduct a larger and more rigorous study to establish the safety and effectiveness of the proposed somatic-autonomic reflex pathway procedure in gaining bladder and bowel control in patients with spina bifida. Additionally, we will systemically evaluate and optimize frequency and location for excitation of the new somatic-autonomic reflex arc to a) gain more insight into the neurorecovery associated with nerve rerouting, and b) scientifically and systematically determine the ideal stimulation parameters to achieve best voiding results and make the somatic-autonomic reflex pathway rerouting most useful for the patients. Achieving the aims outlined in this proposal will help firmly establish the procedure as safe and effective, and revolutionize the treatment of bladder and bowel dysfunction in patients with spina bifida. PUBLIC HEALTH RELEVANCE: Spina Bifida, a congenital defect of the spinal cord, causes nerve damage resulting in bowel, bladder and sexual dysfunction. Dr. Xiao, in China, developed a new procedure to rewire the nerves affecting the bladder, and this project aims to scientifically establish the safety and effectiveness of the surgical procedure.