Mark,

I have posted extensively about Dr. Xiao's operation in the past and Jawaid's thread seems to be a good excuse to re-summarize the procedure, what it is and how it may work.

Dr. ChuanGao Xiao is a urologist from Tungji University in Wuhan. He developed a procedure where he takes an anterior spinal root from one of the lumbar segments and connects this to the pudendal nerve that innervates the bladder. In the 1990's, he developed this procedure in rats on Long Island, where he connected the L4 ventral root to the L6 ventral root. When he scratched the skin of the rat, he was able to initiate bladder voiding in the rats [1]. Later, working with one of the top American bladder physiologists (Chuck DeGroat), he published an important paper in the Journal of Urology in 1999, defining the morphology and physiology of this "skin-to-bladder" pathway created by anastomosing the L7 to S1 ventral root. By the way, the rat has 7 lumbar roots (humans have 5). In 2003, Xiao [3] published a paper reporting his experiene with doing this procedure in 15 patients. Two-thirds of the patients recovered bladder control. He then published several neurophysiological studies in animals and humans detailing the mechanisms by which the skin-to-bladder pathway may work [4-6]. In 2005, Xiao [7] published a paper reporting the operation in 20 children with spina bifida, report successful outcomes in 5/6 children with spastic bladders and 12/14 with areflexic (flaccid) bladders. Note that these are papers published in highly regarded western journals and many were co-authored with DeGroat, the most respected name in bladder physiology.

I have heard him present his work on several occasions. In these presentations, he shows men who are able to urinate by scratching themselves on the skin. By the way, he says that children who have spinal bifida and incomplete spinal cord injury are often able to recover some voluntary control of their urination. He has done several hundred cases by now and has been training surgeons from the United States to do the procedure.

Wise.

Published References
Xiao CG and Godec CJ (1994). A possible new reflex pathway for micturition after spinal cord injury. Paraplegia 32: 300-7. Department of Urology, Long Island College Hospital, SUNY Health Science Center at Brooklyn 11201. In order to restore bladder function after spinal cord injury, a controllable new reflex pathway has been established in rats. It involves a somatic reflex arc with an artificially modified efferent branch which passes the somatic motor impulses to the bladder. This is achieved by intradural microanastomosis of the left L4 ventral root to L6 ventral root, while leaving the L4 dorsal root intact as a starter of micturition. The 'skin-CNS-bladder' reflex pathway is designed to initiate voiding by scratching the skin. After axonal regeneration, 15 of the 24 rats with the new pathway underwent electrophysiological study. Single stimuli (0.3-3 mA, 0.02-0.2 ms duration) to the left L4 nerve resulted in evoked potentials (0.5-1 mV) recorded from the left L6 nerve distal to the anastomosis. The bladder detrusor contraction was very quickly initiated by trains of the stimuli and bladder pressures increased rapidly to levels similar to controls. Neural tracing study with horseradish peroxidase (HRP) on six rats with the pathway demonstrated that the somatic motor axons regenerated successfully into the pelvic nerve, and the bladder was reinnervated by the L4 somatic motor neurons. The bladder contraction can also be initiated by electrostimulation of left sciatic nerve as well as scratching the L4 related skin. A new concept may be derived from the skin-CNS-bladder reflex pathway: the impulses delivered from the efferent neurons of a somatic reflex arc can be transferred to initiate responses of an autonomic effector.

Xiao CG, de Groat WC, Godec CJ, Dai C and Xiao Q (1999). "Skin-CNS-bladder" reflex pathway for micturition after spinal cord injury and its underlying mechanisms. J Urol 162: 936-42. Department of Urology, the Long Island College Hospital, SUNY Health Science Center at Brooklyn, New York 11203, USA. PURPOSE: A "skin-CNS-bladder" reflex pathway for inducing micturition after spinal cord injury has been established in cat. This reflex pathway which is basically a somatic reflex arc with a modified efferent limb that passes somatic motor impulses to the bladder, has been designed to allow spinal cord injured patients to initiate voiding by scratching the skin. MATERIALS AND METHODS: The skin-CNS-bladder reflex was established in the cat by intradural microanastomosis of the left L7 ventral root (VR) to the S1 VR while leaving the L7 dorsal root (DR) intact to conduct cutaneous afferent signals that can trigger the new micturition reflex arc. After allowing 11 weeks for axonal regeneration, urodynamic, pharmacological and electrophysiological studies were conducted in pentobarbital or chloralose anesthetized animals. RESULTS: A detrusor contraction was initiated at short latency by scratching the skin or by percutaneous electrical stimulation in the L7 dermatome. Maximal bladder pressures during this stimulation were similar to those activated by bladder distension in control animals. Electrophysiological recording revealed that single stimuli (0.3 to 3 mA, 0.02 to 0.2 msec duration) to the left L7 spinal nerve in which the efferent axons had degenerated evoked action potentials (0.5 to 1 mV) in the left S1 spinal nerve distal to the anastomosis. In addition, increases in bladder pressure were elicited by trains of the stimuli (5 to 20 Hz, 5 seconds) applied to the L7 spinal nerve. Urodynamic studies including external sphincter EMG recording demonstrated that the new reflex pathway could initiate voiding without detrusor-external urethral sphincter dyssynergia. Atropine (0.05 mg./kg., i.v.) or trimethaphan (5 mg./kg., i.v.), a ganglionic blocking agent, depressed the bladder contractions elicited by skin stimulation. The skin-CNS-bladder reflex could also be elicited after transecting the spinal cord at the L2-L3 or L7-S1 levels. CONCLUSION: The cross-wired somato-autonomic bladder reflex is effective in initiating bladder contractions and coordinated voiding in cats with an intact neuraxis and can also induce bladder contractions after acute transection of the lumbar spinal cord. The new pathway is mediated by cholinergic transmission involving both nicotinic and muscarinic receptors. It is concluded that somatic motor axons can innervate bladder parasympathetic ganglion cells and thereby transfer somatic reflex activity to the bladder smooth muscle.

Xiao CG, Du MX, Dai C, Li B, Nitti VW and de Groat WC (2003). An artificial somatic-central nervous system-autonomic reflex pathway for controllable micturition after spinal cord injury: preliminary results in 15 patients. J Urol 170: 1237-41. Department of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. xiaocg@mails.tjmu.edu.cn. PURPOSE: Neurogenic bladder dysfunction after spinal cord injury (SCI) is a major medical and social problem for which there is no definitive solution. After the successful establishment in animals of a skin-central nervous system-bladder reflex pathway for micturition we performed this procedure on 15 patients with SCI who had 3 years of followup. MATERIALS AND METHODS: A total of 15 male volunteers with hyperreflexic neurogenic bladder and detrusor external sphincter dyssynergia (DESD) caused by complete suprasacral SCI underwent limited hemilaminectomy and ventral root (VR) micro anastomosis, usually between the L5 and S2/3 VRs. The L5 dorsal root was left intact as the trigger of micturition after axonal regeneration. Mean followup was 3 years. All patients underwent urodynamic evaluation before surgery and during followup. RESULTS: Preoperative studies in patients with complete suprasacral SCI revealed hyperreflexic neurogenic bladders and DESD with some differences in storage function during infusion cystometrograms. Of the 15 patients 10 (67%) regained satisfactory bladder control within 12 to 18 months after VR micro anastomosis. Average residual urine decreased from 332 to 31 ml and urinary infection as well as overflow incontinence disappeared. Urodynamic studies revealed a change from detrusor hyperreflexia with DESD and high detrusor pressure to almost normal storage and synergic voiding without DESD. Impaired renal function returned to normal. Two patients (13%) who required a skin stimulator to evoke voiding following the VR anastomosis had partial recovery but more than 100 ml residual urine. One patient was lost to followup and 2 had failure. CONCLUSIONS: An artificial somatic-central nervous system-autonomic reflex arc can be established surgically to provide a novel method for controlling bladder function in patients with complete suprasacral SCI who have hyperreflexic bladder and DESD. Nerve impulses delivered from the efferent neurons of a somatic reflex arc can be transferred to initiate the response of an autonomic effector.

Dai CF and Xiao CG (2005). Electrophysiological monitoring and identification of neural roots during somatic-autonomic reflex pathway procedure for neurogenic bladder. Chin J Traumatol 8: 74-6. Department of Orthopedic Surgery, Shenzhen People's Hospital, Jinan University School of Medicine, Guangdong 518020, China. OBJECTIVE: To identify and separate the ventral root from dorsal root, which is the key for success of the artificial somatic-autonomic reflex pathway procedure for neurogenic bladder after spinal cord injury (SCI). Here we report the results of intra-operating room monitoring with 10 paralyzed patients. METHODS: Ten male volunteers with complete suprasacral SCI underwent the artificial somatic-autonomic procedure under general anesthesia. Vastus medialis, tibialis anticus and gastrocnemius medialis of the left lower limb were monitored for electromyogram (EMG) activities resulted from L4, L5, and S1 stimulation respectively to differentiate the ventral root from dorsal root. A Laborie Urodynamics system was connected with a three channel urodynamic catheter inserted into the bladder. The L2 and L3 roots were stimulated separately while the intravesical pressure was monitored to evaluate the function of each root. RESULTS: The thresholds of stimulation on ventral root were 0.02 ms duration, 0.2-0.4 mA, (mean 0.3 mA+/-0.07 mA), compared with 0.2-0.4 ms duration, 1.5-3 mA (mean 2.3 mA+/-0.5 mA) for dorsal root (P<0.01) to cause revoked potentials and EMG. Electrical stimulation on L4 roots resulted in the EMG being recorded mainly on vastus medialis, while stimulation on L5 or S1 roots caused electrical activities of tibialis anticus or gastrocnemius medialis respectively. The continuous stimulation for about 3-5 seconds on S2 or S3 ventral root (0.02 ms, 20 Hz, and 0.4 mA) could resulted in bladder detrusor contraction, but the strongest bladder contraction over 50 cm H2O was usually caused by stimulation on S3 ventral root in 7 of the 10 patients. CONCLUSIONS: Intra-operating room electrophysiological monitoring is of great help to identify and separate ventral root from dorsal root, and to select the appropriate sacral ventral root for best bladder reinnervation. Different parameters and thresholds on different roots are the most important factors to keep in mind to avoid damaging the roots and to assure the best results.

Liu Z, Liu CJ, Hu XW, Du MX and Xiao CG (2005). [an electrophysiological study on the artificial somato-autonomic pathway for inducing voiding]. Zhonghua Yi Xue Za Zhi 85: 1315-8. Department of Urology, Xiehe Hospital, Tongji Medical College, Huanzhong University of Science and Technology, Wuhan 430022, China. OBJECTIVE: To investigate the possibility of regeneration of somatic motor nerve to replace splanchnic nerve and the electrophysiologic characters of the regenerated nerve. METHODS: An artificial somato-autonomic reflex pathway was established by intradural microanastomosis of L(4) ventral root (VR) to L(6)VR at the left side in 12 male Wistar rats. Then the L(4)VR proximal to the anastomosis was stimulated by silver electrode and the evoked potentials were recorded on the distal end to the anastomosis, pelvic nerve and postganlionic fibers of the major pelvic ganglia (MPG). Cystometrography was used to record the intravesical pressure. Hexamethonium, a cholinergic ganglion blocker, was given directly on the pelvic ganglion so as to observe the change of the intravesical pressure evoked by stimulation of the nerves. Another 12 rats were used as controls. RESULTS: (1) In the experimental group, stimulation of the L(4)VR proximal end to the anastomosis evoked potentials on the distal end, the pelvic nerve, and the postganglionic fibers of the MPG, and induced bladder contraction. Stimulation of the contralateral sciatic nerve failed to evoke change of intravesical pressure. In the control group stimulation of the L(4)VR or sciatic nerve failed to evoke potentials on the postganglionic fibers of pelvic nerve and change of intravesical pressure. (2) Stimulation of the ipsilateral sciatic nerve led to an increase of intravesical pressure. (3) After the use of hexamethonium stimulation of the ipsilateral sciatic nerve and proximal end of L(4)-L(6) anastomosis failed to evoke change of intravesical pressure. (4) The conduction velocity of the regenerated motor axons was 33.3 m/s +/- 6.9m/s, significantly higher than that of the control group (11.6 m/s +/- 1.6 m/s). CONCLUSION: Somatic motor axons can regenerate to the MPG and reinnervate the bladder and the impulses from the somatic motor neurons can initiate voiding.

Sievert KD, Xiao CG, Hennenlotter J, Seibold J, Merseburger AS, Kaminskie J, Nagele U and Stenzl A (2005). [voluntary micturition after intradural nerve anastomosis]. Urologe A 44: 756-61. Klinik fur Urologie, Universitat Tubingen. Karl.Sievert@med.uni-tuebingen.de. INTRODUCTION: One of the major challenges in neuro-urology is the restoration of voluntary voiding in a patient after spinal cord injury (SCI). ANIMAL EXPERIMENTS: The earliest reports on reconstruction of urinary bladder function by bridging nerve roots from above the SCI to the below this level were published by Carlsson and Sundin 1968. In another approach, a possible reflex pathway below the SCI to reinitiate voluntary voiding was investigated. The result was a modified somatic reflex arc rostral to the sacral spinal micturition center. FUTURE RESEARCH: Medical reports in numerous publications are still very enthusiastic about the possibility of cell or gene therapy. Such results report the successful bridging of small nerve gaps. The latest approach is the intravenous application of stem cells to aid the recovery of the SCI. CLINICAL APPROACH: The first reports on attempts to reconstruct the nervous pathways to the bladder in patients were published 1967. In two cases, a nerve anastomosis from Th(12) (the lowest intact segment) to S(2+3), bilaterally to the SCI, allowed spontaneous micturition after 8-12 months with reported sensitivity at the base of the penis. With a modification in surgical technique, another group reported a success rate of 100% using the anastomosis of intercostal nerves Th(11+12) to sacral roots S(2+3) to establish a reflex voiding and, in 72% of patients, reappearance of the bulbocavernous and cremaster reflexes. Xiao et al. published, with a 3 year follow-up, the creation of a micturition reflex through anastomosing the ventral roots of L(5) to S(2/3) in complete SCI patients with a 67% success rate a year after surgery. CONCLUSION: There is still a great deal of work required before cell therapy becomes a therapeutic option. Today, the published data strongly suggest that it is possible to treat first line urinary bladder dysfunctions in SCI or spina bifida patients. Before one of these techniques becomes widely used, it should be proven effective in specialized institutions, such as the Department of Urology in collaboration with the Department of Neurosurgery at the University of Tuebingen, Germany.

Xiao CG, Du MX, Li B, Liu Z, Chen M, Chen ZH, Cheng P, Xue XN, Shapiro E and Lepor H (2005). An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida. J Urol 173: 2112-6. Departments of Urology, Tongji Medical College, Xiehe Hospital, Huazhong University of Science and Technology, Wuhan, China. xiaocg@mails.tjmu.edu.cn. PURPOSE: Neurogenic bladder is a major problem for children with spina bifida. Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic. We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying. We report our experience with this procedure in 20 children with spina bifida. MATERIALS AND METHODS: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis. The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration. All patients underwent urodynamic evaluation before and after surgery. RESULTS: Preoperative urodynamic studies revealed 2 types of bladder dysfunction- areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence. Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding. In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any improvement. CONCLUSIONS: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida.

Xiao CG (2006). Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord injury or spina bifida. Eur Urol 49: 22-8; discussion 28-9. Department of Urology, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xiaocg@mails.tjmu.edu.cn. Neurogenic bladder caused by SCI or spina bifida is a major problem. Research in restoring functional micturition has mainly focused on electrical stimulation for many decades with good progress, but it is still not the definitive solution for majority of the SCI patients. An alternative approach has been to investigate restoring innervation to the lower urinary tract after spinal SCI. Different animal and clinical studies were reviewed historically in this article, focused on mainly cross over nerve surgery for reinnervation of the bladder. An artificial somatic-autonomic reflex pathway procedure and its mechanisms were introduced. Clinical application and the satisfactory results of the new procedure were reviewed in details in restoring voluntary bladder control in patients with SCI or spina bifida.

Wang HZ, Li SR, Wen C, Xiao CG and Su BY (2007). Morphological changes of cholinergic nerve fibers in the urinary bladder after establishment of artificial somatic-autonomic reflex arc in rats. Neurosci Bull 23: 277-81. Department of Neurobiology, Third Military Medical University, Chongqing 400038, China. OBJECTIVE: To establish an artificial somatic-autonomic reflex arc in rats and observe the following distributive changes of neural fibers in the bladder. METHODS: Adult Sprague-Dawley rats were randomly divided into three groups: control group, spinal cord injury (SCI) group, and reinnervation group. DiI retrograde tracing was used to verify establishment of the model and to investigate the transport function of the regenerated efferent axons in the new reflex arc. Choline acetyltransferase (ChAT) in the DiI-labeled neurons was detected by immunohistochemistry. Distribution of neural fibers in the bladder was observed by acetylcholine esterase staining. RESULTS: DiI-labeled neurons distributed mainly in the left ventral horn from L3 to L5, and some of them were also ChAT-positive. The neural fibers in the bladder detrusor reduced remarkably in the SCI group compared with the control (P < 0.05). After establishment of the somatic-autonomic reflex arc in the reinnervation group, the number of ipsilateral fibers in the bladder increased markedly compared with the SCI group (P < 0.05), though still much less than that in the control (P < 0.05). CONCLUSION: The efferent branches of the somatic nerves may grow and replace the parasympathetic preganglionic axons through axonal regeneration. Acetylcholine is still the major neurotransmitter of the new reflex arc. The controllability of detrusor may be promoted when it is reinnervated by the pelvic ganglia efferent somatic motor fibers from the postganglionic axons.