Interaction between neurotransmitter antagonists and effects of sacral neuromodulation in rats with chronically hyperactive bladder

OBJECTIVE: To investigate to what extent antagonists of spinal neurotransmitters interact with the effects of sacral neuromodulation in a rat model of a chronically hyperactive urinary bladder. MATERIALS AND METHODS: In female rats the urinary bladder was instilled with turpentine oil 2.5% to induce cystitis. After surviving for 10 days the rats were anaesthetized with urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed in the sacral foramina bilaterally. The spinal cord was exposed by a laminectomy, and a small pool was placed on the cord for intrathecal administration of neurotransmitter antagonists. Sacral neuromodulation was applied before and after administering the antagonists. The antagonists used were: memantine, an antagonist for N-methyl-D-aspartate (NMDA) receptors; CNQX, an antagonist for non-NMDA receptors, and L-NAPNA, a blocker of nitric oxide synthase. RESULTS: With no electrical neuromodulation, memantine and L-NAPNA abolished the cystitis-induced bladder contractions for approximately 4 and approximately 37 min, respectively. The effect of CNQX was similar to that of artificial cerebrospinal fluid. Electrical sacral modulation with no antagonists also transiently abolished the bladder contractions; at the highest intensity used, the pause was 2-3 min. Superfusion of the spinal cord with CNQX reduced this effect of neuromodulation significantly, whereas memantine had no influence, and L-NAPNA increased the neuromodulation-induced pause. CONCLUSIONS: The results suggest that non-NMDA receptors are involved in the effects of sacral neuromodulation, whereas NMDA receptors appear to have no role. Nitric oxide is essential for maintaining the chronic hyperactive state of the urinary bladder.     

Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention

Sacral foramen neuromodulation – initially applied for the treatment of urinary incontinence – has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with α-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6–S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2–5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7–10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a “rebound” phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.     

Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model

Uninhibited bladder contractions are a problem in spinal cord injured patients. Accordingly, methods using electrical stimulation to inhibit the bladder were investigated in chronic spinal cord injured (C6-T1) male cats. In unanesthetized, restrained animals, spontaneous bladder contractions were observed after the bladder was filled above the micturition threshold. In 3 of the 5 cats studied, this bladder activity could be inhibited with stimulation of either sacral nerves or pudendal nerves. Pudendal nerve stimulation, however, was more selective than sacral nerve stimulation for inhibition with fewer side effects such as leg spasms. Tibial nerve stimulation was ineffective and caused leg spasms and increased bladder activity. Finally, high-frequency stimulation (1,000 Hz) of the sacral nerves was shown to block bladder contractions in 2 of 3 cats investigated. However, this method had adverse side effects such as leg flexion and secondary bladder contractions. We conclude that pudendal nerve/pelvic floor stimulation at low frequency is a relatively effective method in this model.     

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.     

Chronic sacral neuromodulation for treatment of neurogenic bladder dysfunction: long-term results with unilateral implants

Objectives. To investigate the therapeutic value of sacral neuromodulation in patients with neurogenic disorders in whom conservative treatment options were unsuccessful. Neurogenic disorders may result in various forms of lower urinary tract dysfunction.Methods. Twenty-seven patients (19 women, 8 men) aged 18 to 63 years (mean 44.9 years) were subjected to percutaneous test stimulation of the sacral spinal nerves. Their urologic symptoms consisted of bladder storage failure (n = 15) due to detrusor hyperreflexia and/or bladder hypersensitivity, failure to empty due to detrusor areflexia (n = 11), and combined bladder hypersensitivity and detrusor areflexia (n = 1). Twelve patients (11 women and 1 man) underwent chronic sacral neuromodulation with unilateral electrode implantation into one of the dorsal S3 foramina. The follow-up was 89.3 months (range 13 to 126).Results. Severe side effects were encountered in 2 patients (1 with infection and 1 with adverse sensation during stimulation) and moderate side effects in another 3 patients. In 1 patient, the implant had to be removed during the immediate postoperative period. In 3 patients, the implant was not effective. In 8 patients, the symptoms of lower urinary tract dysfunction were significantly attenuated (50% or more) for 54 months (range 11 to 96). After this period, all implants became ineffective, except one, which was still in use at the last follow-up visit.Conclusions. Unilateral chronic sacral neuromodulation using sacral foramen electrodes can be a valuable, but only temporary, treatment for neurogenic bladder dysfunction. The technique of chronic sacral neuromodulation should be refined to achieve the same and lasting results with implantation systems as achieved with preoperative test stimulation.     

Sakrale Neuromodulation in der Urologie

Sacral nerve modulation (SNM) is an innovative, minimally invasive treatment that uses chronic low-level electrical stimulation of the sacral plexus to recruit residual physiological function of urinary bladder detrusor, pelvic floor muscles, and the anorectal continence structures. Classic indications for sacral neuromodulation in urology are refractory overactive bladder symptoms (urinary urgency ± incontinence) and chronic nonobstructive urinary retention. SNM also offers a therapeutic alternative in refractory chronic pelvic pain syndrome. The exact mechanism of action is still unknown, but it is assumed that electrical stimulation of the sacral nerves leads to neuromodulation as well as clinically beneficial effects in the pelvic floor, the sphincter complex, and the distal colorectum. SNM is a multistep procedure. In a test phase of so-called percutaneous or peripheral nerve evaluation (PNE), the effect of sacral neuromodulation is evaluated over days or weeks during which a bladder diary/pain protocol is kept. The predictive value of PNE is high, while morbidity and surgical trauma are low. The screening phase provided by PNE makes this technique unique and offers an ideal instrument for patient selection. After final implantation of the neurostimulator (InterStim II), the long-term success rate is over 60–90%. At our clinic, 42 patients underwent a PNE procedure between January 2009 and June 2010. Of these, 34 patients had a >50% success rate and had been implanted with the InterStim II device (80.9%). The success rates were 83% for overactive bladder and 89% for chronic retention (mean follow-up 7.8 months). In addition to the surgical procedure, the exact indication and postoperative care are important prerequisites of successful therapy. To date, no information on the number of implanted stimulators in Germany is available. This suggests the need for establishment of a national prospective registry. It would also be appropriate that the experts from the implantation centers form a working group.     

Neurostimulation for lower urinary tract voiding problems

In 1981, Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery-powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department, chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesicourethral dysfunction in 55 patients with a mean postoperative follow-up of 44.3 months. Lasting symptomatic improvement of more than 50% was achieved in 16 of 21 patients with motor urge incontinence (76.2%) and in 22 of the 28 patients with urinary retention (78.6%). In our opinion, chronic sacral neuromodulation offers a sustained therapeutic effect to treatment responders that is not achieved by temporary neuromodulation techniques. Chronic neuromodulation should be considered predominantly in patients with urinary retention and in patients with motor urge incontinence who refuse temporary techniques or who require too much effort to achieve a sustained clinical effect.     

Detection and inhibition of hyperreflexia-like bladder contractions in the cat by sacral nerve root recording and electrical stimulation

Detection of bladder volume and hyperreflexive bladder contractions would be useful in individuals with overactive bladders. We sought to determine whether bladder filling and/or reflex bladder contractions could be detected by electrical recording from the sacral nerve roots, and whether bladder contractions could be inhibited by stimulation of sacral afferents. Six male cats were anesthetized with alpha-chloralose and bipolar cuff electrodes were used to measure sacral nerve root electroneurograms (ENG) during slow bladder filling, during rapid injections of fluid into the bladder, and during hyperreflexia-like bladder contractions. The rectified and time-averaged activity of the S1 extradural root increased by 0-5 % above the baseline during bladder filling. Rapid injections caused a sudden increase in bladder pressure, and a 3-36 % increase over baseline in the S1 nerve activity. Withdrawal of the same volume caused a reduction in pressure and a decrease in recorded activity (4-14 %). At the onset of a bladder contraction, there was a 7-38 % increase over baseline in the S1 nerve activity. This activity increase was sustained for the duration of the contraction and decreased during bladder relaxation. The onset and duration of bladder contractions could be detected consistently from these nerve activity changes. Recording only afferent activity showed that the increased nerve activity was due to S1 sensory rather than motor fibers. In two cats, it was demonstrated that an ongoing bladder contraction could be inhibited by rectal distension. In one cat, the contractions could be terminated by electrical stimulation of the S1 dorsal root. The results demonstrate that afferent sacral root nerve activity can be used to detect hyperreflexive bladder contractions at low bladder pressures. Such a signal might be used to trigger bladder inhibition via electrical stimulation of specific sacral afferents.     

Analysis of bladder related nerve cuff electrode recordings from preganglionic pelvic nerve and sacral roots in pigs

PURPOSE: Electrical stimulation of appropriate lower urinary tract (LUT) nerves may be used in bladder dysfunction to achieve continence and abolish hyper-reflexic detrusor contractions. It can also be used for consequent emptying of the bladder. To control the time course of the described functional phases, knowledge of bladder sensory information is needed. We investigated if the latter could be extracted from the LUT nerve activity. MATERIALS AND METHODS: In acute experiments using 10 pigs, tripolar cuff electrodes were placed unilaterally around the pelvic nerve and the S3 and S2 roots. The cuff electrode signals, filling rate and the bladder and rectal pressures were recorded during slow and fast bladder fillings/emptyings. RESULTS: Two pigs were excluded from the analysis because of no observed changes in the nerve signals in one animal, and because of electrical noise problems in the other animal. Fast bladder pressure increases resulted in a sudden pelvic nerve signal rise in 6 out of 7 pigs (3 out of 6 for the S3 nerve signal). Slow bladder pressure increase was reflected in the recorded nerve activity only in 3 out of 8 and in 3 out of 7 pigs for the pelvic and S3 cuff signals respectively. In 2 animals small spontaneous bladder contractions were clearly reflected in the pelvic nerve signal (contractions were observed only in 3 pigs). Except in one pig, there were no slow/fast bladder filling responses recorded in the S2 roots. It is shown that the recorded responses were afferent. CONCLUSIONS: Cuff electrodes can be used to record bladder afferent information from the pelvic nerve and the sacral root S3 in pig. Pelvic nerve recordings were more selective than the sacral root recordings. Nerve activity increases were more distinct and repeatable during rapid bladder pressure changes and small spontaneous bladder contractions than during slow bladder fillings.     

The use of electrical devices for the treatment of bladder dysfunction: a review of methods

PURPOSE: We reviewed the literature on the application of various devices and techniques for the electrical stimulation treatment of lower urinary tract dysfunction with respect to mechanism of action and clinical outcome. MATERIALS AND METHODS: A systematic review was done in PubMed of publications on intravesical stimulation, direct bladder stimulation, stimulation of the pelvic and pudendal nerves, transcutaneous-electrical nerve stimulation, stimulation of the sacral spine and roots, and lower limb stimulation. RESULTS: It is difficult truly to compare different treatment modalities because there are hardly any randomized placebo controlled studies. Also, there is considerable variety in treatment parameters and schedules reported as well as in criteria for success. Nevertheless, it can be said that electrical neurostimulation and neuromodulation result in a 30% to 50% clinical success on an intent to treat basis. Influencing lower urinary tract innervation at the level of sacral roots seems successful in neurological and nonneurological cases. It has the advantage of pretesting possibilities to improve patient selection and treatment outcome with the obvious drawback of invasiveness. Noninvasive techniques lack screening tests, making patient selection a matter of trial and error, and when there is success patients almost always need maintenance therapy. CONCLUSIONS: Randomized clinical trials to compare different techniques and evaluate placebo effects are urgently needed, as are further studies to elucidate modes of action to improve stimulation application and therapy results. The introduction of new stimulation methods may provide treatment alternatives as well as help answer more basic questions on electrical neurostimulation and neuromodulation.     

Effects of stimulation site and stimulation parameters on bladder inhibition by electrical nerve stimulation

What's known on the subject? and What does the study add? Electrical stimulation of the dorsal nerve of the penis, the compound pudendal nerve and the S1 sacral nerve have been used clinically to treat the symptoms of overactive bladder, but the relative efficacy of the three locations was unclear and the optimal stimulation parameters across locations had not been determined. In the present paper we quantified the effects of acute electrical stimulation location, frequency and amplitude on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats. Our results could influence the selection of anatomical targets for clinical neuromodulation and how neuromodulation devices are programmed.

OBJECTIVE

• ? To quantify the effects of acute electrical stimulation frequency and amplitude at the dorsal nerve of the penis (DNP), pudendal nerve (PN) and S1 sacral nerve (S1) on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats.

MATERIALS AND METHODS

• ? Experiments were conducted in 14 adult male cats anaesthetized with α‐chloralose.
• ? The effects of stimulation on the pressure – time integral of reflex bladder contractions were evaluated using a randomized block design with the following factors randomized: stimulation intensity (0.8, 1, or 2× the threshold for evoking a reflex electromyogram response in the external anal sphincter [T]), frequency (2 Hz, 5 Hz, 7.5 Hz, 10 Hz, 15 Hz, 20 Hz, or 33 Hz) and location (PN, S1 or DNP).
• ? The effects of stimulation (with parameters that produced maximum inhibition of isovolumetric bladder contractions) on cystometric capacity were evaluated using a randomized block design, with the order of stimulation location randomized and control trials interleaved with stimulation trials.

RESULTS

• ? Inhibition of isovolumetric bladder contractions was significantly dependent on stimulation location, frequency, amplitude and the interactions between any two of these variables.
• ? Stimulation of the DNP, at 5 Hz, 7.5 Hz or 10 Hz, and at 2T caused greater reductions in normalized bladder contraction area than any other location, frequency or amplitude tested.
• ? Stimulation of the PN or S1 at 7.5 Hz or 10 Hz and 2T, or of the DNP at 5 Hz, 7.5 Hz or 10 Hz and 0.8T, 1T or 2T generated maximum inhibition of isovolumetric bladder contractions.
• ? Cystometric capacity was significantly larger with stimulation (10 Hz, 1T–2T) than control.
• ? There was no significant difference in cystometric capacity based upon stimulation location.

CONCLUSIONS

• ? There was no significant difference in the maximum degree to which the respective optimum parameters inhibited bladder contractions or increased cystometric capacity by location.
• ? The range of amplitudes and frequencies that caused maximum inhibition was larger for DNP stimulation than for PN or S1 stimulation.
• ? These findings have implications on the selection of anatomical target and device programming for clinical neuromodulation for treatment of the symptoms of overactive bladder.

     

Surface stimulation techniques for bladder management in the spinal dog

Electrical stimulation of the bladder wall or sacral nerves may be effective for bladder management in the spinal cord injured patient. However, extensive surgery has been required for electrode implantation. We compared urodynamic responses using surface and minimally invasive epidural stimulating techniques in the chronic spinal male dog. Various surface stimulating techniques were effective: 1) sacral monopolar electrical stimulation with negative electrodes over S2 sacral foramina and positive electrodes on the legs, 2) sacral bipolar electrical stimulation with electrodes only over sacral foramina, 3) perineal monopolar electrical stimulation, and 4) perineal tactile stimulation. Urodynamic responses were similar to those for sacral epidural electrodes implanted adjacent to sacral nerves. Voiding was obtained both during stimulation and poststimulation. Stimulating parameters that were effective for daily voiding with sacral surface electrodes were 10 pps, 30 to 45 ma, 0.6 ms pulse duration, and 2 to 5 sec stimulation train duration.     

Changes in brain activity following sacral neuromodulation for urinary retention

PURPOSE: Sacral nerve stimulation (neuromodulation) can restore bladder sensation and the ability to void in women with urinary retention due to sphincter overactivity (Fowler's syndrome). Modulation of central afferent activity is considered critical to this therapeutic effect but the neural mechanisms are poorly understood. Therefore, we undertook a functional brain imaging study to determine how neuromodulation acts on brain centers involved in the representation and control of bladder function. MATERIALS AND METHODS: Eight patients with Fowler's syndrome and 8 healthy controls underwent brain imaging with positron emission tomography to identify regions of brain activity relating to the perception of bladder fullness and their modulation by sacral nerve stimulation. RESULTS: In healthy controls bladder fullness enhanced activity in brainstem (midbrain) and limbic cortical regions. Women with urinary retention showed no significant brainstem activity but did show enhanced limbic cortical activity when the bladder was full in the absence of neuromodulation. Neuromodulation restored a normal pattern of midbrain activity and decreased cortical activity in this group. CONCLUSIONS: Our study provides novel neuroimaging evidence for the existence of abnormal interaction between brainstem and cortical centers in women with urinary retention. Furthermore, we have been able to show evidence that the therapeutic effect of sacral neuromodulation is achieved through restoration of activity associated with brainstem autoregulation and attenuation of cingulate activity.     

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.     

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.     

Neuromodulation reduces c-fos gene expression in spinalized rats: a double-blind randomized study

PURPOSE: Neuromodulation of the sacral nerve roots is effective to treat various voiding dysfunctions, but the underlying mechanism of neuromodulation is not known. The objective of this study is to evaluate whether inhibition of afferent c-fiber activity is the underlying mechanism of sacral nerve root neuromodulation. MATERIALS AND METHODS: Twenty-nine female Sprague-Dawley rats weighing 220 to 250 gm. were divided into 4 groups: normal control (normal rats without any procedure; n = 5), sham with saline (spinalized rats at T9 with saline bladder instillation; n = 7), sham with acetic acid (spinalized rats at T9 with acetic acid bladder instillation; n = 8) and stimulation group (spinalized rats at T9 with acetic acid bladder instillation plus electrical stimulation; n = 9). A cystometrogram was performed 10 days after spinal cord transection to confirm the development of bladder hyperreflexia. Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 hours a day for three weeks. The rats were perfused with 4% paraformaldehyde and an immunocytochemical method was used to stain fos-protein that was encoded by c-fos gene. A double-blind method was used in counting fos-protein positive neurons. RESULTS: Bladder hyperreflexia developed in all spinalized rats 10 days after spinal cord transection. Peak bladder pressure was found significantly reduced after neuromodulation (30.4 +/- 4.2 cm. water) compared with the same rats before neuromodulation (82.4 +/- 10.2 cm. water; p = 0. 007). The number of fos-protein positive neurons in the L6 spinal cord segment in the neuromodulation group (93.2 +/- 13.3 cells/section) decreased significantly when compared with the sham with acetic acid group (160.6 +/- 25.0 cells/section; p = 0.02). There was no significant difference in c-fos expression between the sham with saline group (90.5 +/- 15.6 cells/section) and the neuromodulation group (p = 0.92). CONCLUSIONS: Sacral dorsal root neuromodulation reduces c-fos gene expression and bladder hyperreflexia in spinalized rats, through inhibition of afferent c-fiber activity.     

Successful use of sacral neuromodulation after failed bladder augmentation

Sacral neuromodulation has become a standard minimally invasive therapy for refractory urinary urge/frequency and urge incontinence. Prior to the widespread use of sacral neuromodulation, augmentation cystoplasty was a standard treatment for refractory overactive bladder (OAB). The use of sacral neuromodulation following bladder augmentation has not been previously reported in the literature. We report 2 cases of successful sacral neuromodulation in patients with OAB refractory to bladder augmentation.     

Functional magnetic stimulation of the spinal cord--a urodynamic study in healthy humans

AIMS: To study the effects of functional magnetic stimulation of the spinal cord in healthy subjects on somatic and autonomic pathways innervating the anal and the external urethral sphincter, bladder, bladder neck, and rectum. METHODS: Eight healthy male volunteers gave their written informed consent and underwent functional magnetic stimulation of the thoracolumbar and sacral spinal cord. A two-channel microtip pressure transducer catheter was placed rectally measuring the abdominal and anal sphincter pressure. A three-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder, the bladder neck, and the external urethral sphincter pressure. A comprehensive protocol of single and repetitive magnetic stimulations was performed. Frequency, location, and duration of stimulation were varied while the intensity of stimulation was adapted to the maximum the subjects could tolerate. In four subjects, the degree of bladder filling was changed and the protocol was repeated when the subjects reported a full bladder and desire to void. RESULTS: Continuous magnetic stimulation of the thoracolumbar spinal cord and the sacral roots applied with different frequencies (5, 15, 30, 60, 100 Hz) and different duration of stimulation (10, 30, 120 sec) evoked sphincter contraction of both anal and urethral sphincters. The stimulation could not evoke contractions of the bladder, the bladder neck, or the rectum. Also with filled bladder and present desire to void, the magnetic stimulation could not activate autonomic pathways innervating these structures. CONCLUSIONS: Considering our results, we suggest that in individuals with preserved sensibility magnetic stimulation of the spinal cord with intensities below the pain threshold is ineffective in activating autonomic nerve fibres innervating bladder, bladder neck, and rectum.     

The role of neuromodulation in the management of urinary urge incontinence

OBJECTIVE: To examine the benefit-risk profile of neuromodulation in treating refractory urinary urge incontinence and other voiding disorders. PATIENTS AND METHODS: The outcome measures from all patients in pivotal clinical trials who had undergone sacral nerve stimulation were analysed retrospectively. RESULTS: Neuromodulation was effective in several clinical studies; the response is durable and the benefit-risk profile good. CONCLUSION: Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes.     

Neuromodulation through sacral nerve roots 2 to 4 with a Finetech-Brindley sacral posterior and anterior root stimulator

STUDY DESIGN: Investigation of five patients receiving an implant, using laboratory cystometry and self-catheterisation at home. OBJECTIVES: To use the established Finetech-Brindley sacral root stimulator to increase bladder capacity by neuromodulation, eliminating the need for posterior rhizotomy, as well as achieving bladder emptying by neurostimulation. SETTING: Spinal Injuries Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. METHODS: Five patients underwent implantation of a Finetech-Brindley stimulator without rhizotomy of the posterior roots. This was either a two channel extradural device (four cases) or a three channel intrathecal device (one case). In each patient, the implant was configured as a Sacral Posterior and Anterior Root Stimulator (SPARS). Postoperatively, repeated provocations using rapid instillation of 60 ml saline were used to determine the relative thresholds for neuromodulation using each channel. The effect of continuous neuromodulation was examined in the laboratory using slow fill cystometrograms, and conditional stimulation was also studied (neuromodulation for 1 min to suppress hyperreflexic contractions as they occurred). In one patient, neuromodulation was applied continuously at home, and volumes at self catheterisation recorded in a diary. RESULTS: Reflex erections were preserved in each patient. In three patients, detrusor hyperreflexia persisted postoperatively and neuromodulation via the implant was studied. In these three patients, the configuration was: S2 mixed roots bilaterally (channel B), and S34 bilaterally (channel A). Both channels could be used to suppress provoked hyperreflexic contractions, with the S2 channel effective at a shorter pulse width than S34 in a majority of cases. Continuous stimulation more than doubled bladder capacity in two out of three patients during slow fill cystometry. Conditional stimulation was highly effective. In the one patient who used continuous stimulation at home, bladder capacity was more than doubled and the effect was comparable with anticholinergic medication. Bladder pressures >70 cm water could be achieved with intense stimulation in three patients, but detrusor-external urethral sphincter dyssynergia (DSD) prevented complete emptying. CONCLUSIONS: Neuromodulation via a SPARS was effective and may replace the need for posterior rhizotomy. However, persisting DSD may prevent complete bladder emptying and warrants further investigation.