Intradural sacral rhizotomies and implantation of an anterior sacral root stimulator in the treatment of neurogenic bladder dysfunction after spinal cord injury

Summary Hyperreflexia of the detrusor is an important problem in the treatment of dysfunction of the lower urinary tract after spinal cord injury. Many treatment modalities have been proposed but they mostly give only temporary relief or are accompanied by severe side effects. In 1969, Brindley started animal experiments to accomplish intradural electrical stimulation of the sacral roots. A serially produced intradural sacral root stimulator that has been available since 1986 enables electrostimulation of the appropriate sacral roots that is sufficient to induce bladder emptying. The combination of the implantation of this stimulator with a complete intradural sacral posterior rhizotomy from S2 to S4/S5 appears to be an interesting treatment modality for the hyperreflexic bladder after spinal cord injury. The surgical technique is described, as are the postoperative care and the possible complications.     

Clinical applications of electrical stimulation after spinal cord injury

During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development.     

Functional electrical stimulation of bladder and bowel in spinal cord injury

The purpose of this collective review is to examine the use of functional electrical stimulation for incontinence. The Finetech-Brindley bladder system enhances voiding through stimulation via electrodes implanted around the ventral sacral roots. Detrusor hyperreflexia is eliminated through complete dorsal rhizotomy, which results in loss of reflex defecation and reflex erection/reflex lubrication. Consequently, a new system is being devised in which functional electrical stimulation for incontinence in spinal cord injury can be achieved without dorsal rhizotomy.     

Neurosurgical treatment of hyperactive bladder in spinal cord injury patients

OBJECTIVES: We report long-term results of posterior sacral root rhizotomies in combination with Finetech-Brindley anterior sacral root stimulators implanted intradurally in 20 spinal cord injury patients. MATERIAL: and methods: The 14 female and 6 male patients included 14 paraplegics and 6 tetraplegics. All of them initially presented hyperactive bladder, detrusor-sphincter dyssynergia, recurrent urinary tract infection and performed (self) intermittent catheterization. Prior to implantation, an intrathecal test using bupivacaine was performed to confirm the compliances of the bladder. The main indication for implantation was persistent urinary incontinence refractory to medical therapy. RESULTS: After implantation the mean follow-up was 4,5 years. In all, 18 patients used the stimulator alone for bladder emptying and 18 patients were completely continent. The mean bladder capacity increased from 190 ml preoperatively to 460 ml after the operation. The mean residual urinary volume was reduced from 90 ml to 25 ml. No changes were noted by renal isotopic scanning in upper urinary tracts of patients. In 1 patient, a second extradural implant was performed. DISCUSSION: This article also include an overview of a) the different available sites where application of electrical stimulation results in a detrusor contraction, b) the benefits and disadvantages of the sacral posterior rhizotomy, c) selective stimulation techniques that allow selective detrusor activation by sacral root stimulation. CONCLUSION: Sacral anterior root stimulation combined with sacral posterior rhizotomy is a valuable method to restore bladder functions in spinal cord injured patients suffering from hyperactive bladder refractory to medical therapy.     

Staggered rhizotomy of anterior and posterior sacral roots for bladder reservoir function in spinal cord injury: a canine experimental study and preliminary clinical report

Objective: To report an experimental study and preliminary clinical results of staggered anterior and posterior sacral rhizotomy for restoring function of the bladder and preventing reflex incontinence in supra‐conal spinal cord injury (SCI). Methods: Ten T10 spinal cord transected mongrel dogs were divided into three groups. In group 1 (n= 2), laminectomy only was performed (control). In group 2 (n= 4), all L7‐S3 posterior roots were microsurgically cut (complete deafferentation). And in group 3 (n= 4), the L7, S1, S3 posterior roots and S2 anterior root were cut (staggered deafferentation and deefferentation). Intraoperative electrical stimulation and postoperative cystometrography (CMG) were carried out. In the clinic, three patients with spastic bladder caused by a supra conal complete SCI underwent staggered rhizotomy and were followed up for 6 years. Results: In the canine experimental study, resection of the S2 anterior root combined with L7, S1 and S3 posterior rhizotomy, stimulating the S2 posterior root (four dogs) resulted in a minimal rise in pressure in the bladder and urethra, which was only about 10% of that obtained by stimulating the S2 proximal posterior root while its anterior counterpart was intact (eight dogs, Student's t‐test, P < 0.01). The CMG study showed that groups 2 and 3 had similar volume/pressure curves; in both groups the tendency was to develop flaccid bladders. In the clinic, three cases underwent staggered rhizotomy of the anterior and posterior roots in S3 and S4. Good bladder reservoir and compliance was achieved over six years of follow‐up. Conclusion: Staggered rhizotomy of the anterior and posterior sacral roots at different spinal cord levels has the same denervation effect as a complete posterior rhizotomy, and good bladder reservoir function can be achieved by this procedure.     

Electrical Stimulation of the Urethra Evokes Bladder Contractions in a Woman With Spinal Cord Injury

Abstract

Objective: Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI.

Case Report: A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction.

Findings: Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation.

Conclusions: This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.     

Clinical Applications of Electrical Stimulation After Spinal Cord Injury

Abstract

Summary: During the last one-half century, electrical stimulation has become dinically significant for improving health and restoring useful function afterspinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed musdes and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated indude reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. lmprovement of cough has also been demonstrated. Stimulation of intact sacral ne.rves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. lt is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function . Useful hand grasp can be provided in CS and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation afterspinal cord injury and identifies some future directions of research and dinical and commercial development.     

Electrical Stimulation of the Urethra Evokes Bladder Contractions in a Woman With Spinal Cord Injury

Objective:

Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI.

Case Report:

A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction.

Findings:

Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation.

Conclusions:

This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.     

光感基因调控技术对大鼠骶上脊髓损伤后膀胱尿动力学和肌电图的影响

目的观察光感基因调控技术对大鼠骶上脊髓损伤所致神经源性膀胱功能的影响。方法 50只大鼠经尿流动力学检查无异常后进行随机分组,并采用T10脊髓完全横断建立脊髓损伤动物模型,分为假手术对照组、脊髓损伤无蓝光刺激组和脊髓损伤蓝光刺激组。2周后进行膀胱尿动力学、肌电图测定。结果脊髓损伤蓝光刺激组大鼠膀胱逼尿肌肌条舒缩曲线大部分可见规律性变化,波形均匀一致;同时膀胱最大容量增加,内压降低,顺应性升高;而脊髓损伤无蓝光刺激组无上述变化。结论光感基因可以调节骶上脊髓完全性损伤后膀胱逼尿肌的收缩功能,对神经源性膀胱功能恢复有重要意义。     

Results of the Treatment of Neurogenic Bladder Dysfunction in Spinal Cord Injury by Sacral Posterior Root Rhizotomy and Anterior Sacral Root Stimulation

Purpose

We evaluated the results of treatment of neurogenic bladder dysfunction in spinal cord injury by sacral posterior root rhizotomy and anterior sacral root stimulation using the Finetech-Brindley stimulator.**Finetech Ltd., Welwyn Garden City, Hertfordshire, England.

Materials and Methods

In 52 patients with spinal cord lesions and urological problems due to hyperreflexia of the bladder complete posterior sacral root rhizotomy was performed and a Finetech-Brindley sacral anterior root stimulator was implanted. All patients were evaluated and followed with a strict protocol. A minimal 6-month followup is available in 47 cases.

Results

Complete continence was achieved in 43 of the 47 patients with 6 months of followup. A significant increase in bladder capacity was attained in all patients. Residual urine significantly decreased, resulting in a decreased incidence of urinary tract infections. In 2 patients upper tract dilatation resolved. In 3 patients rhizotomy was incomplete and higher sectioning of the roots was necessary. One implant had to be removed because of infection.

Conclusions

The treatment of neurogenic bladder dysfunction in spinal cord injury by anterior sacral root stimulation with the Finetech-Brindley stimulator in combination with sacral posterior root rhizotomy provides excellent results with limited morbidity.     

Optimization of Sacral Ventral Root Stimulation Following SCI: Two Case Reports with Six-Month Follow-Up

Abstract

Sacral ventral root stimulation in conjunction with sacral dorsal rhizotomy has been effective in promoting voiding in individuals with upper-motor-neuron spinal cord injury. We report on two patients who had variable voiding responses to stimulation during the first six months after electrode implantation. We used videourodynamic records and daily voiding records to characterize their voiding difficulties. Different methods were used to improve voiding, including seating adjustments and changes in stimulation parameters. The first patient was unable to empty his bladder on a regular basis with stimulation using 24 pulses per sec stimulating frequency for the first two months after implantation. Voiding was substantially improved by using 35 pulses per sec. At the end of six months, he is regularly emptying his bladder with stimulation and is on an every-second-day bowel program. However, his bowel program has been irregular. The second patient had very good voiding when stimulation was applied in bed, but he had poor voiding with high residual volumes when sitting in his wheelchair. Voiding was improved when he used a wheelchair cushion that was cut out in the back or lifted his buttocks off the chair. These procedures appeared to reduce perineal pressures. This patient has bowel care on alternate days and his bowel care time has been reduced following implantation of the device. Neither of the patients experienced an erection with the device. Both patients feel positive about their implant experience.     

The Effect of Thigh Muscle Reconditioning by Electrical Stimulation on Urodynamic Activity in SCI Patients

ABSTRACT

Various forms of electrical stimulation are being used more frequently for bladder and muscle rehabilitation following spinal injury. Fifteen patients with spinal cord injury underwent a four to eight week period of thigh muscle reconditioning by surface electrical stimulation. The accumulated effects of this program on bladder function were assessed by urodynamic evaluation before and after the test period. Seven patients had beneficial changes of either an increase in bladder capacity and/or a decrease in bladder pressure. Six patients had a decrease in bladder capacity and/or an increase in bladder pressure, although two of these six patients had resolution of spinal shock. Two patients with detrusor areflexia had no changes in pressure or capacity. There was no change in the basic urodynamic patterns, only the parameters of bladder capacity and pressure. Increasing the use of electrical stimulation for rehabilitation of the spinal cord population might alter bladder function, although not consistently. One should, therefore, be aware of these changes when setting up such rehabilitation programs.     

骶神经根电刺激排尿中完全性后根去传入的替代方法

目的 探讨脊髓损伤病人进行骶神经根电刺激排尿时膀胱完全性去传入手术的替代方法。方法 １０条犬经Ｔ１０平面截瘫后,按Ｌ７～Ｓ３前后根切断程度和组合方式的不同分成４组,观察术中神经根电刺激时膀胱尿道的压力变化和术后膀胱压力容积曲线（ＣＭＧ）变化。结果 保留２侧Ｓ１前后根完整,电刺激同平面Ｓ１的总根或后根,膀胱尿道的压力反应相同;切断两侧Ｓ１前根,刺激同平面的Ｓ１后根,膀胱尿道的压力反应显著降低,仅为前     

Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview

Structural discontinuity in the spinal cord after injury results in a disruption in the impulse conduction resulting in loss of various bodily functions depending upon the level of injury. This article presents a summary of the scientific research employing electrical stimulation as a means for anatomical or functional recovery for patients suffering from spinal cord injury. Electrical stimulation in the form of functional electrical stimulation (FES) can help facilitate and improve upper/lower limb mobility along with other body functions lost due to injury e.g. respiratory, sexual, bladder or bowel functions by applying a controlled electrical stimulus to generate contractions and functional movement in the paralysed muscles. The available rehabilitative techniques based on FES technology and various Food and Drug Administration, USA approved neuroprosthetic devices that are in use are discussed. The second part of the article summarises the experimental work done in the past 2 decades to study the effects of weakly applied direct current fields in promoting regeneration of neurites towards the cathode and the new emerging technique of oscillating field stimulation which has shown to promote bidirectional regeneration in the injured nerve fibres. The present article is not intended to be an exhaustive review but rather a summary aiming to highlight these two applications of electrical stimulation and the degree of anatomical/functional recovery associated with these in the field of spinal cord injury research.     

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control.     

Selective sacral rhizotomy in the management of the reflex neuropathic bladder: a report on 17 patients with long-term followup.

During the last 6 years 24 patients with cervical or thoracic spinal cord injuries and a severe reflex neuropathic bladder underwent selective dorsal sacral rhizotomy with the aid of intraoperative neurostimulation and urodynamic monitoring. Preoperative and postoperative evaluation was available in 17 patients. Followup ranged from 2 months to 5 years (mean 32 months). Mean bladder capacity increased significantly after rhizotomy (from 148 +/- 28.1 to 377 +/- 52.9 ml., p less than 0.001), as did mean volume to first contraction (from 99 +/- 28.6 to 270 +/- 39.3 ml., p less than 0.001). No significant changes in bowel or erectile function were noted. Continence was improved in 94%, with 14 patients remaining completely dry and voiding with electrical stimulation or intermittent self-catheterization. The long-term results of selective sacral rhizotomy compare favorably to more aggressive alternatives, such as augmentation cystoplasty or urinary diversion.     

Anatomical feasibility of anastomosing intercostal nerves (D10&D11) and subcostal nerve (D12) to S2 ventral root and lumbar plexus for management of bladder function after spinal cord injury

ObjectiveThe transfer of peripheral nerves originating above the level of injured spinal cord into the nerves/roots below the injury is a promising approach. It facilitates the functional recovery in lower extremity, bladder/bowel and sexual function in paraplegics. We assessed anatomical feasibility of transfer of lower intercostal nerves to S2 ventral root in human cadaver for management of neurogenic bladder dysfunction in patients with spinal cord injury.MethodsStudy was performed in five formalin fixed cadavers. Cadavers were placed in prone position. A transverse incision was made along 11th ribs on both sides and 10th, 11th Intercostal nerves (ICN) and subcostal nerve were harvested up to maximum possible length. In four cadavers the ventral root of S2 was exposed by endoscope and in one by the standard open laminectomy. Intercostal nerves were brought down to lumbo-sacral region, S2 ventral root was cut cranially and feasibility of intercostal to S2 anastomosis was assessed.ResultsThe mean length of intercostal nerves was 18.4 cm for the 10th 19.5 cm for the 11th and 22.15 cm for the subcostal nerve. The length of harvested nerve and the nerve length necessary to perform sacral roots neurotization were possible in all cases by only by subcostal nerve while T11 and T10 ICN fall short of the required length.ConclusionFor Spinal cord lesions located at the conus, subcostal nerve could be connected to ventral root of S2 in an attempt to restore bladder function while 10th and 11th ICN had enough length to neurotize lumbar plexus.     

Development of less invasive neuromuscular electrical stimulation model for motor therapy in rodents

Abstract

Background

Combination therapy is essential for functional repairs of the spinal cord. Rehabilitative therapy can be considered as the key for reorganizing the nervous system after spinal cord regeneration therapy. Functional electrical stimulation has been used as a neuroprosthesis in quadriplegia and can be used for providing rehabilitative therapy to tap the capability for central nervous system reorganization after spinal cord regeneration therapy.

Objective

To develop a less invasive muscular electrical stimulation model capable of being combined with spinal cord regeneration therapy especially for motor therapy in the acute stage after spinal cord injury.

Methods

The tibialis anterior and gastrocnemius motor points were identified in intact anesthetized adult female Fischer rats, and stimulation needle electrodes were percutaneously inserted into these points. Threshold currents for visual twitches were obtained upon stimulation using pulses of 75 or 8 kHz for 200 ms. Biphasic pulse widths of 20, 40, 80, 100, 300, and 500 µs per phase were used to determine strength–duration curves. Using these parameters and previously obtained locomotor electromyogram data, stimulations were performed on bilateral joint muscle pairs to produce reciprocal flexion/extension movements of the ankle for 15 minutes while three-dimensional joint kinematics were assessed.

Results

Rhythmic muscular electrical stimulation with needle electrodes was successfully done, but decreased range of motion (ROM) over time. High-frequency and high-amplitude stimulation was also shown to be effective in alleviating decreases in ROM due to muscle fatigue.

Conclusions

This model will be useful for investigating the ability of rhythmic muscular electrical stimulation therapy to promote motor recovery, in addition to the efficacy of combining treatments with spinal cord regeneration therapy after spinal cord injuries.     

骶神经根选择性切断治疗截瘫后痉挛性膀胱的实验及临床研究

目的观察高选择性骶神经根前根切断术治疗脊髓损伤后痉挛性膀胱的疗效,探讨其治疗机制、最佳手术方法及临床实际疗效. 方法雄性家犬12只,制成脊髓损伤后痉挛性膀胱模型,根据骶神经根切断方式:切断S2前根,切断S2前根 S3 1/2前根,切断S2、S3前根,完全切断S2～4神经根,依序分为A、B、C、D 4个组,通过尿动力学检测及电生理观察,分析比较骶神经根切断前、后各组功能性指标的变化,确定其最佳手术方案.临床治疗则根据实验结果,选择性切断脊髓损伤后痉挛性膀胱患者S2前根或 S3 1/2前根共32例.术前膀胱容量平均(120±30) ml,术前排尿量平均(100±30) ml,尿道压力平均为(120±20) cm H2O. 结果 4个组术后膀胱容量分别为:(150±50)、(180±50)、(230±50)、(400±50) ml;排尿量分别为:(130±30)、(180±50)、(100±50)、(50±30) ml.临床治疗32例,术后膀胱容量平均增加至410 ml左右,排尿量平均增加至350 ml左右,所有患者尿失禁消失.有13例获22个月远期随访,无复发. 结论高选择性骶神经根切断治疗脊髓损伤后痉挛性膀胱疗效显著,是一种值得研究、推广的新方法.     

Functional reinnervation of the canine bladder after spinal root transection and genitofemoral nerve transfer at one and three months after denervation

ABSTRACT In the immediate management of patients with spinal cord injury (SCI), patients are typically observed for a period of time to determine whether voluntary control of bladder function returns. Therefore, bladder reinnervation surgeries are not likely to be performed immediately after the injury. We performed genitofemoral to pelvic nerve transfer (GF NT) surgery in canines at 1 and 3 months after bladder denervation (transection of S1 and S2 spinal roots) to determine whether this type of bladder reinnervation surgery has potential clinical feasibility. Nerve cuff electrodes were implanted on the genitofemoral nerves proximal to the pelvic nerve transfer site. Evidence for bladder reinnervation includes (1) increased bladder pressure and urethral fluid flow following electrical stimulation in four out of 20 nerve cuff electrodes implanted on the transferred GF nerves, (2) bilateral pelvic nerve stimulation induced bladder pressure and urethral fluid flow in three of four denervated animals with 1-month delay GF NT, and in five of six denervated animals with 3-month delay GF NT, and (3) abundant L1 and L2 spinal cord cell bodies (the origin of the GF nerve) retrogradely labeled with fluorogold injected into the bladder in all 10 of the GF NT animals, except one animal on one side. This study presents initial proof of concept that GF NT is a potentially viable clinical approach to reinnervation of the lower motor neuron-lesioned urinary bladder.