Conditional neuromodulation of neurogenic detrusor overactivity using transrectal stimulation in patients with spinal cord injury: A proof of principle study

Aims

A proof of principle study of a novel wearable device to control neurogenic detrusor over‐activity in eight male spinal cord injured subjects using conditional neuromodulation.

Methods

Transrectal stimulation was delivered through the device in response to simultaneously recorded external anal sphincter (EAS) contraction as a marker for neurogenic detrusor overactivity (NDO). The effect of conditional neuromodulation on bladder capacity and maximum detrusor pressure was investigated in addition to reliability of dyssynergic sphincter contraction as a marker for NDO.

Results

Conditional neuromodulation through the novel device showed a statistically significant increase in bladder capacity and reduction in maximum detrusor pressure in six male subjects with spinal cord injury (SCI). EAS activity was a reliable surrogate for detection of NDO.

Conclusions

It has been shown for the first time that conditional neuromodulation can be delivered and triggered via a single biocompatible device placed in the anal canal. The pudendal nerves lying in Alcock's canal were stimulated through the wall of the anal canal, and the dyssynergic activity of the EAS was used to detect NDO and trigger neuromodulation giving significant increases in bladder capacity and reduction in detrusor pressure in six male subjects with SCI.     

Event driven electrical stimulation of the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in multiple sclerosis

AIMS: The aim of this study was to evaluate the effect of automatic event driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in patients suffering from Multiple Sclerosis. METHODS: A total of 10 patients participated in the study. Detrusor pressure was recorded during physiological filling of the bladder and electrical stimulation was applied with surface electrodes whenever the detrusor pressure exceeded 10 cm H(2)O. RESULTS: In seven of the eight patients, where neurogenic detrusor overactivity was observed an average of 12 detrusor contractions could be inhibited by stimulation. In one patient, however, stimulation failed to inhibit the detrusor contractions. The average increase in bladder volume from first suppressed detrusor contraction until leakage was 94% (range: 22-366%). On average, the time from first suppressed contraction until leakage was 15 min and 50 sec (range: 4 min 58 sec-32 min 5 sec) with an average physiological filling rate of 8 ml/min. Urgency was effectively suppressed at the onset of stimulation. CONCLUSIONS: The results indicate that involuntary detrusor contractions in patients with multiple sclerosis can effectively be inhibited with event driven stimulation, hereby improving bladder capacity and reducing the number of incontinence episodes. However, the used method for detecting detrusor contractions is not suitable in a chronic setting and alternative techniques needs to be investigated if stimulation should be applied automatically.     

Control of the unstable urinary bladder by graded thermoelectric cooling of the spinal cord

OBJECTIVE: To evaluate local lumbosacral spinal-cord cooling (a novel technique for neuromodulating urinary bladder reflexes) for its feasibility in possible clinical use, by determining the efficacy and the optimum temperature for suppressing reflex urinary incontinence in two rat models of neurogenic urinary bladder instability. MATERIALS AND METHODS: Overactivity of the detrusor muscle was induced by inflammation of the urinary bladder in a group of rats. A second group of rats was examined 6 weeks after complete midthoracic spinal cord transection, when all animals had developed neurogenic bladder hyper-reflexia. The intravesical pressure, urethral pressure and electromyographic (EMG) activity of the external urethral sphincter (EUS) were recorded simultaneously during repetitive local cooling and re-warming of the dorsal L6/S1 spinal cord segments, using a thermoelectric cooling device. RESULTS: Spinal cord cooling at L6/S1 had no influence on the recorded values at >26 degrees C, but markedly suppressed detrusor contraction frequency at 21- 25 degrees C. Cooling to <20 degrees C completely and reversibly eliminated inflammation-induced bladder contractions in rats with an intact neural axis and significantly reduced the contraction amplitudes (mean reduction 61%) and duration of contractions in spinally transected rats. Cooling simultaneously increased tonic EUS EMG activity and urethral perfusion pressure in both experimental groups, indicating closure of the urethral outlet. Cooling of adjacent spinal cord segments had no influence on bladder and urethral functions. CONCLUSION: Cooling the dorsal spinal cord at the origin of the parasympathetic innervation of the bladder can be used to reversibly suppress bladder instability with simultaneous closure of the urethral outlet. Therefore, local spinal cord cooling, e.g. as an implantable thermoelectric device, may offer a suitable method to treat detrusor overactivity and restore continence.     

Closed loop electrical control of urinary continence

PURPOSE: Individuals with spinal cord injury or neurological disorders may have neurogenic detrusor contractions at low volumes (bladder hyperreflexia), which cause incontinence and can lead to significant health problems. Bladder contractions can be suppressed by electrical stimulation of inhibitory pathways but continuous activation may lead to habituation of the inhibitory reflex and loss of continence. We determined whether conditional stimulation with electrical stimulation of inhibitory pathways applied only at the onset of nascent bladder contractions allows the bladder to fill to a greater volume before continence is lost compared with continuous stimulation. MATERIALS AND METHODS: In 6 alpha-chloralose anesthetized cats cystometry was performed to compare the volume at which continence was lost under the conditions of no stimulation, continuous stimulation and conditional electrical stimulation of inhibitory pathways. PNT ENG was used to detect the onset of bladder contractions and it served as the input to an event triggered control system that regulated conditional stimulation to maintain continence. RESULTS: Conditional stimulation controlled by PNT ENG increased bladder capacity by 36% over no stimulation and by 15% over continuous stimulation (p <0.001 and 0.027, respectively). The event triggered control system decreased stimulation time by 67% compared to continuous stimulation. CONCLUSIONS: Conditional electrical stimulation of inhibitory pathways is more effective than continuous stimulation. A control system triggered by PNT ENG can maintain urinary continence.     

Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with MS

OBJECTIVES: The aim of this study was to investigate whether acute electrical stimulation of the posterior tibial nerve could suppress detrusor contractions in multiple sclerosis (MS) patients with neurogenic detrusor overactivity. METHODS: Two successive slow-fill cystometries (16 ml/min) were carried out in eight MS patients with neurogenic detrusor overactivity. The first filling served as control without stimulation. In the second filling, electrical stimulation using needle electrodes was applied automatically to the posterior tibial nerve when the detrusor pressure exceeded 10 cm H(2)O. An additional filling in which the needle electrodes were replaced by surface electrodes was carried out in three patients. RESULTS: The control filling showed detrusor overactivity in eight patients, but electrical stimulation of the posterior tibial nerve failed to suppress detrusor contractions in all tested patients. CONCLUSIONS: Although neuromodulative effects may be obtained with therapeutic electrical stimulation of the posterior tibial nerve, no acute effects were demonstrated. For this reason, electrical stimulation of pudendal afferents remains the only option if acute suppression of a detrusor contraction is required.     

Electrical stimulation of sacral dermatomes in multiple sclerosis patients with neurogenic detrusor overactivity

AIMS: Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may introduce hygienic challenges. The aim of this study was to assess whether electrical stimulation of the sacral dermatomes could suppress detrusor contractions in multiple sclerosis (MS) patients with NDO, hereby providing an alternative to DPN stimulation. MATERIALS AND METHODS: A total of 14 MS patients (8 M, 6 F) with low bladder capacity (<300 ml) and a recent urodynamic study showing detrusor overactivity incontinence participated in the study. Three successive slow fill cystometries (16 ml/min) were carried out in each patient. The first filling served as control filling where no stimulation was applied. In the second and third filling electrical stimulation of either the DPN or sacral dermatomes was applied automatically whenever the detrusor pressure exceeded 10 cmH2O. RESULTS: The control filling showed detrusor overactivity in 12 of the 14 patients. In 10 of the 12 patients one or more detrusor contractions could be suppressed with DPN stimulation. Electrical stimulation of the sacral dermatomes failed to suppress detrusor contractions in all patients. CONCLUSIONS: Although therapeutic effects may be present from stimulation of the sacral dermatomes, we were unable to demonstrate any acute effects during urodynamics. For this reason stimulation of the sacral dermatomes is not an option in a system that relies on the acute suppression of a detrusor contraction.     

Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study

PURPOSE: We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy. MATERIALS AND METHODS: A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment. RESULTS: In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup. CONCLUSIONS: In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.     

Treatment of neurogenic detrusor overactivity in spinal cord injured patients by conditional electrical stimulation

PURPOSE: The feasibility of automatic event driven electrical stimulation of the dorsal penile/clitoral nerve in the treatment of neurogenic detrusor overactivity (NDO) was evaluated in individuals with spinal cord injury. MATERIALS AND METHODS: The study included 2 women and 14 men older than 18 years with NDO, bladder capacity below 500 ml and complete or incomplete suprasacral spinal cord injury. Detrusor pressure (Pdet) was recorded during ordinary, natural bladder filling. In a similar subsequent recording Pdet was used to trigger electrical stimulation when pressure exceeded 10 cm H2O. RESULTS: Of the 16 patients enrolled in this study 13 had increased bladder capacity together with a storage pressure decrease as a result of automatic, event driven electrical stimulation. In 2 patients stimulation could not inhibit the first undesired contraction, leakage occurred and finally 1 could not tolerate stimulation. During stimulated filling Pdet never exceeded 55 cm H2O. Thus, storage pressure was sufficiently low to prevent kidney damage. An average bladder capacity increase of 53% was achieved. CONCLUSIONS: This study demonstrates the feasibility of automatic, event driven electrical stimulation in the treatment of NDO. Although the setup in this experiment is not suitable in a clinical setting, the treatment modality is promising and it warrants further investigation.     

Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury

AIMS: Although electrical stimulation of the pudendal nerve has been shown to evoke reflex micturition-like bladder contractions in both intact and spinalized cats, there is little evidence to suggest that an analogous excitatory reflex exists in humans, particularly those with spinal cord injury (SCI). We present two cases where electrical activation of pudendal nerve afferents was used to evoke excitatory bladder responses. SUBJECTS AND METHODS: A percutaneously placed catheter electrode was used to electrically stimulate the pudendal nerve trunk in two males with SCI. The response was quantified with recorded changes in detrusor pressure and EMG activity of the external anal sphincter. RESULTS: In both individuals, frequency specific (f = 20-50 Hz) activation of the pudendal nerve trunk evoked excitatory bladder contractions that also depended on the stimulus amplitude and bladder volume. CONCLUSION: The results suggest that selective activation of the perineal branches of the pudendal nerve may further augment the excitatory reflex evoked by electrical stimulation.     

Conditional stimulation of the dorsal penile/clitoral nerve may increase cystometric capacity in patients with spinal cord injury

AIMS: To investigate the feasibility of conditional short duration electrical stimulation of the penile/clitoral nerve as treatment for detrusor hyperreflexia, the present study was initiated. METHODS: Ten patients with spinal cord injury, 4 women and 6 men, with lesions at different levels above the sacral micturition center had a standard cystometry performed. During a subsequent cystometry, conditional short duration electrical stimulation of the penile/clitoral nerve was performed as treatment for one or more detrusor hyperreflexic contractions. RESULTS: In all patients, at least one contraction (mean, 7.8; range, 1-16 contractions) was inhibited by the stimulations. The mean cystometric capacity was increased significantly by conditional electrical stimulation, from 210 mL in the control cystometries to 349 mL in the stimulation cystometries (P=0.016). The maximal detrusor pressure during the first contraction in the control cystometries was mean 51 cm H(2)O, whereas the maximal pressure of the first contraction in the stimulation cystometries was reduced to mean 33 cm H(2)O (P=0.045). CONCLUSIONS: The authors conclude that repeated conditional short duration electrical stimulation significantly increased cystometric capacity in patients with spinal cord injury. The increase was caused mainly by an inhibition of detrusor contractions. The need for a reliable technique for chronic bladder activity monitoring is emphasized, as it is a prerequisite for clinical application of this treatment modality.     

Genital nerve stimulation is tolerable and effective for bladder inhibition in sensate individuals with incomplete SCI

Background: Neurogenic detrusor overactivity after spinal cord injury (SCI) causes urinary incontinence and reduces bladder capacity. Surface electrical genital nerve stimulation (GNS) acutely inhibits reflex bladder contractions. The stimulation amplitude selected for GNS is typically twice the amplitude that is required to evoke the pudendal-anal reflex. There is concern about the ability of persons with sensation to comfortably tolerate effective levels of GNS. The objective of this work is to determine if persons with incomplete SCI are able to tolerate acute GNS for bladder inhibition.

Methods: Twenty-four subjects with neurogenic detrusor overactivity, SCI, and pelvic sensation were enrolled in this case series. The setting was the Spinal Cord Injury Service of a Veterans Affairs Medical Center. Primary outcome measures were sensation threshold and tolerable stimulation amplitude; secondary outcome measures were bladder capacity and bladder contraction inhibition.

Results: GNS was tolerable up to 30±16?mA (range 8?mA to ≥60?mA) at amplitudes greater than twice the pudendal-anal (PA) reflex threshold, which was 8±5?mA (range 4?mA to 20?mA). Twelve subjects tolerated GNS at greater than twice the PA, six tolerated 1–1.5 times the PA, and five had no identifiable PA. GNS at tolerable amplitudes inhibited reflexive bladder contractions or increased bladder capacity 135±109?mL (n=23). GNS did not cause autonomic dysreflexia or intolerable spasticity.

Conclusions: GNS is tolerable at amplitudes that effectively inhibit neurogenic detrusor overactivity in individuals with pelvic sensation. GNS therefore is a tool with potential clinical applications for persons with preserved sensation.     

Does magnetic stimulation of sacral nerve roots cause contraction or suppression of the bladder?

AIMS: The aim of this study was to resolve the paradox as to whether magnetic stimulation of sacral nerve roots results in contraction or suppression of the bladder, in both normal individuals and patients with spinal cord injury (SCI). MATERIALS AND METHODS: Seven males with complete SCI and neurogenic detrusor overactivity (NDO) and five normal males were investigated. Bladder capacity and maximum cystometric capacity were determined, respectively, in these groups. Magnetic stimulation was applied to sacral nerve roots using a multi-pulse magnetic stimulator and coil. Stimulation was applied at half capacity, near-full capacity, and during NDO or voiding (in normal individuals). Single and intermittent bursts of stimulation were applied. RESULTS: Neither single nor intermittent bursts of magnetic stimulation of the sacral nerve roots resulted in significant bladder pressure rises. Occasionally, following cessation of the magnetic stimulation bladder contractions were seen in patients with NDO. These contractions had an unpredictable and variable latency. As previously reported, magnetic stimulation suppressed NDO in patients with SCI, and suppressed voiding in normal individuals. CONCLUSIONS: Bladder contractions are occasionally observed in patients with NDO following withdrawal of stimulation. This phenomenon hypothetically arises as a result of removal of the bladder suppression provided by magnetic stimulation, rather than direct motor pathway stimulation (as has been reported by others). The ability of sacral magnetic stimulation to suppress detrusor contractions is reaffirmed.     

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.     

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。     

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.     

膀胱出口梗阻所致逼尿肌过度活动的神经电生理研究

目的 从膀胱传入神经以及盆底相关神经肌肉角度探讨神经因素及肌源性因素在膀胱出口梗阻所致的逼尿肌过度活动发生中的作用.方法 采用耻骨上膀胱颈梗阻的方法建立逼尿肌过度活动大鼠模型,测定不稳定收缩时盆神经传入电位信号,并同步测定阴部神经运动支电位、尿道外括约肌肌电及腹肌肌电的反射反应.并观察T8段脊髓截断、双侧盆神经截断、腹交感干截断以及双侧阴部神经截断后大鼠膀胱充盈测压不稳定收缩的变化.结果 成功制作了膀胱出口梗阻逼尿肌过度活动大鼠模型,成功率62.5%.充盈性膀胱测压神经肌电生理同步记录结果显示,允盈期逼尿肌过度活动可分为两种类型,一种为收缩幅度高于10 cmH2O(1 cmH2O=0.098 kPa)的逼尿肌过度活动(B-DO),伴有同步盆神经传入的信号明显增强,且能引发阴部神经、尿道外括约和腹肌肌电图出现显著变化;一种为收缩幅度低于10 cmH2O的逼尿肌过度活动(S-DO),没有上述盆神经传入及相关神经肌电变化.T8脊髓截断后,膀胱充盈-排尿收缩周期消失,膀胱基础压显著升高,B-DO消失,S-DO仍然存在,且收缩幅度较截断前略有上升,但差异无统计学意义.依次截断控制膀胱的盆神经、交感神经和阴部神经后,膀胱失去充盈-排尿收缩周期,基础压显著升高,不稳定收缩中B-DO消失,S-DO仍然存在.结论 膀胱出口梗阻所致的逼尿肌过度活动存在不依赖于中枢和周围神经的膀胱源性因素.     

Effect of distigmine combined with propiverine on bladder activity in rats with spinal cord injury

It is not uncommon for patients with spinal cord injury to have both detrusor overactivity during the storage phase and detrusor underactivity during the voiding phase. However, there has been no information about the efficacy of combined treatment with cholinesterase inhibitors and anti-muscarinic agents for this condition. Therefore, the effect of co-administration of distigmine bromide (a cholinesterase inhibitor) and propiverine hydrochloride (an anti-muscarinic agent) on bladder activity was examined in rats with spinal cord injury. Rats were anesthetized with isoflurane and the lower thoracic spinal cord was transected. The bladder was emptied by abdominal compression twice a day for 14 days after surgery. A total of 4 weeks after surgery, the animals were anesthetized with urethane, and the effect of intravenous injection of distigmine (0.01-1 mg/kg) followed by propiverine (1 mg/kg) on continuous cystometry parameters was examined. After injection of distigmine (0.1 and 1 mg/kg), the maximum bladder contraction pressure was significantly increased, and the duration of bladder contraction and the interval between bladder contractions were significantly prolonged. The baseline bladder pressure was not changed by injection of distigmine. After the addition of propiverine, the interval between bladder contractions was significantly further prolonged without any change of the maximum contraction pressure, baseline pressure or duration of bladder contraction. The residual volume after voiding bladder contraction was less than 0.1 mL in all animals. In conclusion, co-administration of distigmine with propiverine might improve both bladder underactivity during the voiding phase and bladder overactivity during the storage phase.     

Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study

PURPOSE: We determined the safety and efficacy of each of 2 doses of botulinum toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin. MATERIALS AND METHODS: A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity (due to spinal cord injury in 53 and multiple sclerosis in 6) requiring clean intermittent self-catheterization were randomized to receive a single dose into the detrusor of BTX-A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of the treatment effect on bladder function. The impact of treatment on quality of life was assessed using the Incontinence Quality of Life questionnaire. RESULTS: There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups (p 相似文献   

Effect of the potassium channel opener WAY-133537 on the overactive bladder of spinalized rats

AIMS: To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were used in this study. Six animals served as normal controls (without spinal cord transaction (ST)), while 42 rats underwent ST at the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was performed in six randomly chosen animals to ensure the development of neurogenic detrusor overactivity. The remaining 36 rats were divided into three equal groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537 0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and treatment group was further divided into two sub-groups (n = 6), with CMG at 3 and 4 weeks after ST, respectively. RESULTS: Two weeks after ST, all "vehicle control" rats developed detrusor overactivity with a mean frequency of 0.96 and 1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2-week treatment, respectively. Neurogenic detrusor overactivity disappeared from 50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor overactivity vanished from 67% of the animals with even further reduction in the frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared from only one animal with a non-significant decline in frequency. Fifty percent of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no detrusor overactivity. CONCLUSIONS: WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.     

Control and coordination of bladder and urethral function in the brainstem of the cat

Stimulation and lesion experiments in the pontine tegmentum of 34 cats, with urodynamic measurements both pre- and peroperatively and during up to 4 months of follow-up, have confirmed the existence of two different brainstem regions concerned with lower urinary tract function. In the dorsolateral pontine tegmentum, a compact, dorsomediolaterally located M region, corresponding to Barrington's micturition centre, reacts specifically to electrical stimulation, causing prompt relaxation of the anal and urethral striated sphincters followed after about 2 s by detrusor contraction, as in normal micturition. Bilateral lesions in this M region lead to a 2–9 week period of urinary retention, during which detrusor activity is depressed and the bladder capacity increases. Stimulation in a larger, more diffuse, more laterally located L region elicits sphincter activity: contraction of the striated urethral sphincter together with an increase in the anal-sphincter EMG, or relaxation of the striated urethral sphincter together with either a decrease or an increase in the anal-sphincter EMG. Provided lethal respiratory complications can be avoided, bilateral lesions in this L region lead after a few days to a state, lasting up to 2 months, in which there is urinary incontinence accompanied by a decrease in the bladder capacity and detrusor overactivity. Neither type of lesion leads to true detrusor-urethra dyssynergia. However, because the amplitude of anal-sphincter EMG sometimes increases when the striated urethral sphincter relaxes, observations of the anal-sphincter EMG can misleadingly suggest dyssynergia. Brainstem mapping of the results of stimulation suggests a motor pathway running from the M to the L region and another descending caudally from the L region. The observations suggest that the M region forms a true micturition centre, facilitating the detrusor voiding contraction and also (via the presumptive connection with the L region) ensuring synergic sphincter relaxation. The L region appears not only to relay this voiding sphincter relaxation, but to be responsible for control of the pelvic floor and its sphincters in general, and for helping to maintain urinary continence.