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

描述(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，腰部以下失去感觉和肌肉功能，导致肠道、膀胱和性功能障碍。患者不能小便或经常尿湿，这种情况在一生中持续存在，导致重大的生活质量和健康问题。通常需要清洁的间歇性导尿来正确排空膀胱。通常需要抗血吸虫药物来缓解可能导致不可逆转的肾脏损害的高尿路压力，而透析或肾移植是维持生命的唯一途径。肖博士在中国身上开发并实施了一种新的手术，将功能正常、健康的腰椎神经根与控制膀胱的骶神经连接起来。最终的结果是产生一种新的反射，通过抓挠或刺激脊神经根供应的皮肤，可以排空膀胱。他报告说，在92名脊髓损伤患者中，88%的患者在神经移位手术后一年内恢复了对膀胱的控制，而在110名患有脊柱裂的儿童中，一年内成功率为87%。然而，对于中国来说，严格的随访是具有挑战性的，因此对于术后神经康复，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取得成功结果中可能发挥的作用，仍有许多未知之处。在博蒙特，一项针对9名脊柱裂受试者的试点研究正在进行中，但目前美国还没有其他中心在研究这项技术。我们的初步数据非常有希望，目前有9名受试者在术后12个月内排尿，7/9的受试者自愿或通过刺激新的反射机制排尿。该项目旨在扩大我们的试点经验，进行更大范围和更严格的研究，以确定拟议的躯体-自主神经反射通路在脊柱裂患者获得膀胱和肠道控制方面的安全性和有效性。此外，我们还将系统地评估和优化新的躯体-自主神经反射弧的兴奋频率和位置，以a)更深入地了解与神经改道相关的神经康复，以及b)科学和系统地确定理想的刺激参数，以达到最佳的排尿效果，使躯体-自主神经反射通路改道对患者最有用。实现这项提案中概述的目标将有助于坚定地确立该手术的安全性和有效性，并彻底改变脊柱裂患者的膀胱和肠道功能障碍的治疗。公共卫生意义：脊柱裂是一种先天性脊髓缺陷，会导致神经损伤，导致肠道、膀胱和性功能障碍。中国的肖医生开发了一种重新连接影响膀胱的神经的新程序，该项目旨在科学地确定手术过程的安全性和有效性。

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.