Unilateral vs bilateral sacral neuromodulation in pigs with formalin-induced detrusor hyperactivity.

OBJECTIVE: To investigate the efficacy of unilateral vs bilateral sacral neuromodulation (SNM) under standard experimental conditions by stimulating the dorsal sacral roots in pigs with formalin-induced detrusor hyperactivity. MATERIALS AND METHODS: After lumbosacral laminectomy in eight alpha-chloralose-anaesthetized Göttinger mini-pigs, the dorsal roots of the nerve S3 were inserted into separate compartments of a size-modified Brindley electrode. Detrusor hyperactivity was induced by intravesical instillation of a 0.25% formalin solution. Stimulation of the separated dorsal roots was performed on the unilateral right, respectively, the unilateral left side, as well as bilaterally and with stimulation off-phases in a randomized pattern. A biphasic rectangular signal (impulse 200 micros, 20 Hz, 2.0 V) was used for SNM. The bladder pressure values were registered on a urodynamic unit and evaluated as contractions and amplitudes per minute. RESULTS: During unilateral stimulation, the mean (sem) number of contractions was reduced significantly from 4.73 (0.66) to 2.73 (0.62). The amplitude was also reduced significantly from 12.86 (1.23) to 8.32 (0.66). By contrast, bilateral stimulation lowered the mean (sem) number of overactive detrusor contractions to 1.08 (1.02) and the amplitude to 3.08 (2.42), which are highly significant reductions. CONCLUSION: In this porcine model, bilateral neurostimulation was a more effective method of SNM than unilateral stimulation. We assume that this is due to the additive effect of stimulating both sides, as well as the greater chance of stimulating the relevant dorsal roots of the sacral nerve fibres. By contrast, unilateral neuromodulation may be only partially effective by not being capable of influencing the entire bladder, or possibly by allowing new formation of neuronal pathophysiological pathways.

Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation.

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Functional outcome following photoselective vaporisation of the prostate (PVP): urodynamic findings within 12 months follow-up.

OBJECTIVES: We determined the impact of potassium-titanyl-phosphate (KTP) laser therapy of the prostate on urodynamic results, voiding function, quality of life, and sexual function. DESIGN, SETTING, AND PARTICIPANTS: Forty-five patients complaining of symptomatic benign prostatic hyperplasia (BPH) and urodynamically proven obstructive voiding were included in the prospective study. Follow-up exams were repeated 3 mo and 12 mo after the treatment. INTERVENTION: All patients underwent photoselective 80-Watt KTP laser vaporisation of the prostate performed by two experienced surgeons. MEASUREMENTS: Disease-specific quality of life and sexual function were assessed using the International Prostate Symptom Score (IPSS) and International Inventory of Erectile Function (IIEF). Video-urodynamics were carried out to determine changes in pressure flow and bladder function. RESULTS AND LIMITATIONS: The average preoperative prostate volume was 47.63 ml (range 30-75 m). The mean preoperative PSA-value, which had been 3.5 ng/ml (range 0.13-7 ng/ml) initially, dropped by 34.2% after 3 mo and 37.1% after 12 mo. Despite transient micturition complaints (40%), all patients showed significant improvement in the IPSS in urinary peak flow and detrusor pressure at peak flow. The mean post-void residual urine volume decreased, while erectile function and libido scores remained unaffected by the procedure according to the IIEF. Detrusor contractility was also not affected in any of the patients. The single-centre study design and small number of patients may have limited the study results. CONCLUSIONS: KTP laser therapy of the prostate achieves significant improvements both symptomatically as well as with respect to objective micturition parameters. The procedure leads to a functional deobstruction of the lower urinary tract with steady improvement results throughout the follow up period.

Facilitatory neuromodulative effect of duloxetine on pudendal motor neurons controlling the urethral pressure: a functional urodynamic study in healthy women.

OBJECTIVE: The aim of this functional urodynamic experiment in healthy women was to study the effect of duloxetine, which is a combined serotonin and norepinephrine (5-HT/NE) reuptake inhibitor, on urethral resting pressure, excitability of pudendal motor neurons, and urethral sphincter contractility. METHODS: In 11 healthy female subjects three baseline urethral pressure profiles (UPPs) were obtained to study resting pressure. Afterward the individual motor threshold (MT) for external urethral sphincter (EUS) contraction in response to transcranial magnetic stimulation (TMS) was determined to study the excitability of pudendal motor neurons. Another three UPPs were recorded while sacral root magnetic stimulation (SMS) was performed to evoke reproducible urethral contractions to study urethral sphincter contractility. Then the women received 40 mg duloxetine and the protocol was repeated 4 h after drug administration. The resting pressure values, MT values following TMS, and the EUS pressure amplitudes in response to SMS obtained at baseline were statistically compared to the corresponding values at follow-up after duloxetine. RESULTS: Oral administration of duloxetine significantly lowered MT for EUS contraction in response to TMS (p=0.013). In addition, duloxetine significantly increased EUS pressure amplitudes in response to SMS (p=0.0007, 5 of 11 subjects evaluated) but did not change urethral resting pressures. CONCLUSIONS: This is the first functional, urodynamic controlled study to show that the combined 5-HT/NE reuptake inhibitor duloxetine has a significant effect on the excitability of pudendal motor neurons and on urethral sphincter contractility in healthy women in vivo but no significant effect on urethral resting tone. Our data confirm a facilitatory neuromodulative effect of duloxetine on sphincter motor neurons in humans.

Preoperatively evaluated bladder wall tension as a prognostic parameter for postoperative success after surgery for bladder outlet obstruction.

OBJECTIVES: To evaluate a novel method for the determination of bladder wall tension (BWT) and to correlate these findings with postoperative persistent residual urine, postoperative uroflow, International Prostate Symptom Score, and quality-of-life index in patients with bladder outlet obstruction. METHODS: In 28 male patients with prostate enlargement or bladder neck sclerosis undergoing surgical treatment, the preoperative BWT was determined after urodynamic investigation and ultrasound determination of bladder weight. The patients were divided into two groups: group 1 (n = 24), postoperative residual urine volume less than 50 mL; and group 2 (n = 4), persistent residual urine volume greater than 50 mL. Five patients in group 1 were unobstructed in accordance with the Abrams-Griffiths nomogram. This group was compared separately with group 2, in which all 4 patients were also classified as unobstructed. RESULTS: The preoperative BWT in group 1 was 5.2 +/- 4.1 N/cm(2), significantly different from the preoperative BWT in group 2 (0.98 +/- 0.3 N/cm(2)). The BWT in the 5 unobstructed patients in group 1 (3.4 +/- 1.3 N/cm(2)) was significantly greater than that in patients in group 2. BWT was the sole parameter that was distinctly different between these 5 patients and the patients in group 2, with a significant influence on postoperative uroflow, International Prostate Symptom Score, and quality-of-life index. CONCLUSIONS: The results of this pilot study show that the determination of BWT allows further evaluation of the detrusor function. Especially in patients classified as unobstructed according to the Abrams-Griffiths nomogram, preoperative determination of the BWT could become a supplemental and important parameter with predictive value for postoperative success in patients with prostate enlargement or bladder neck sclerosis.

Cerebral electrical response on urinary bladder filling: first experimental findings.

Micturition disorders in neurologic diseases are often combined with reduced bladder sensation. Bladder sensation is important to time the void appropriately and to prevent bladder overdistension. We attempted to evaluate cerebral evoked potentials by bladder distension to objectively determine bladder sensation. In six rabbits, cerebral evoked potentials were evaluated by averaging cerebral responses to bladder distension. We stimulated the bladder with a computerized air pump system, resulting in repeated filling and emptying of the bladder. The number of stimulations, stimulation intensity, and different electroencephalograph electrode positions (both mastoids and frontal) were investigated. In all rabbits, cerebral evoked potentials were observed after 500 stimulations when stimulation pressure exceeded a certain threshold. Optimum response was observed after 1,000 stimulations. The latency of response of the frontal electrode position was observed after the mastoidal response with a significant delay of approximately 0.8 seconds. The latencies were significantly different when using different stimulation intensities. At lower intensity (mean pressure, 16.6 mm Hg), the response was observed after 4.531 +/- 0.909 seconds. At higher intensity (mean pressure, 19.0 mm Hg), cerebral response was observed after a latency of 3.971 +/- 0.735 seconds. We conclude that recording of cerebral evoked potentials by bladder distension is possible, resulting in an objective evaluation of afferent pathways from the bladder. In combination with subjective perception of bladder fullness, this finding may be a conceivable basis for a biofeedback training program to recover bladder sensation in patients with reduced bladder sensation.

The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades.

UNLABELLED: Bupivacaine causes muscle damage. However, the myotoxic potency of ropivacaine is still unexplored. Therefore, we performed this study to compare the effects of bupivacaine and ropivacaine on skeletal muscle tissue in equipotent concentrations. Femoral nerve catheters were inserted into anesthetized minipigs, and 20 mL of either bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused over 6 h. Control animals were treated with corresponding volumes of normal saline. Finally, muscle samples were dissected at injection sites. After processing and staining, histological patterns of muscle damage were blindly examined, scored (0 = no damage to 3 = myonecrosis), and statistically analyzed. After normal saline, only interstitial edema was found. Bupivacaine treatment caused severe tissue damage (score, 2.3 +/- 0.7), whereas ropivacaine induced fiber injury of a significantly smaller extent (score, 1.3 +/- 0.8). Furthermore, bupivacaine, but not ropivacaine, induced apoptosis in muscle fibers. In summary, both drugs induce muscle damage with similar histological patterns. Compared with bupivacaine, which induces both necrosis and apoptosis, the tissue damage caused by ropivacaine is significantly less severe. We conclude that ropivacaine's myotoxic potential is more moderate in comparison with that of bupivacaine. IMPLICATIONS: After continuous peripheral nerve blockades, the long-acting local anesthetics bupivacaine and ropivacaine both induce fiber necrosis in porcine skeletal muscle tissue. In comparison with ropivacaine, bupivacaine causes tissue damage of a significantly larger extent and additionally induces apoptosis in skeletal muscle cells.

Restoration of external urethral sphincter function after pudendal nerve end-to-end anastomosis in the male rabbit.

PURPOSE: In this study we rehabilitated external urethral sphincter function by pudendal nerve end-to-end anastomosis after experimental pudendal nerve axotomy in male rabbits. MATERIALS AND METHODS: A total of 17 animals were included in this study, including group 1-a control group of 5 (29.4%), group 2-6 (35.3%) and group 3-6 (35.3%). Animals from group 2 underwent bilateral axotomy and group 3 underwent pudendal nerve end-to-end anastomosis. In all groups we performed urodynamic investigations prior to axotomy, after axotomy or anastomosis, and 14, 42 and 90 days after axotomy or nerve anastomosis. RESULTS: In untreated group 1 control sphincter pressure was 28.5 cm H2O. In group 2 average urethral sphincter pressure was 5.6 cm H2O 14 days after axotomy with only a slight increase to 11.05 cm H2O by day 90. In group 3 external urethral pressure increased to 8.26 cm H2O after 14 days and to 21.32 cm H2O by postoperative day 90. CONCLUSIONS: External urethral sphincter deficiency after bilateral pudendal nerve axotomy demonstrates the primacy of the pudendal nerve in the innervation of the external urethral sphincter. We were able to rehabilitate external urethral sphincter function by performing pudendal nerve end-to-end anastomosis.

Methylene blue staining for nerve-sparing operative procedures: an animal model.

OBJECTIVES: To evaluate methylene blue fiber staining as a method of nerve fiber identification in an animal model, because the maintenance of organ function after surgery depends on exact intraoperative identification of the relevant nerve fibers. METHODS: Brindley electrodes were implanted bilaterally at S3 for sacral anterior root stimulation in six minipigs. For reference, stimulation-induced detrusor contractions were recorded urodynamically. After exposure of the ureterovesical junction on both sides, a 2:8 methylene blue solution was applied to the right side; the left side remained untreated. Bilateral dissection of the ureter from the surrounding tissue for a distance of 4 cm proximal to the ureterovesical junction was performed. The methylene blue-stained nerve fibers on the right side were spared; no particular attention was paid to the nerves on the left. Again, sacral anterior root stimulation-induced detrusor contractions were monitored urodynamically on both sides. Then, the identified nerve fibers on the right were cut intentionally, and the detrusor pressure was recorded again under stimulation. Finally, the dissected nerve structures were evaluated histologically. RESULTS: The reference bladder pressures after unilateral stimulation on the left side before ureter dissection showed a mean detrusor pressure (Pdet) of 19 cm H2O. On the right side, the Pdet was 18 cm H2O. After preparation on both sides, a mean Pdet of 3 cm H2O was recorded after left side stimulation, and a Pdet of 17 cm H2O after right side stimulation. When the stained nerve fibers on the right side were cut, no bladder contractions could be induced. The histomorphology of the stained and dissected structures revealed multiple autonomous nerve fibers and small vessels in connective tissue. CONCLUSIONS: The identification of minute nerve bundles is a tedious and difficult task. The results from our animal model demonstrated that supravital staining of autonomous nerve fibers with methylene blue is a simple and reliable method of identification.

Risk of detrusor denervation in antireflux surgery demonstrated in a neurophysiological animal model.

PURPOSE: Earlier anatomical studies have shown a close connection between the ureterovesical junction and detrusor innervation. It prompted us to develop an animal model to demonstrate the risk of partial or complete impairment of this neuronal connection during antireflux surgery. MATERIALS AND METHODS: Six female Göttinger minipigs were anesthetized and laminectomized. After placement of the S3 sacral nerves into separate electrode compartments of a modified Brindley electrode the lower urinary tract was exposed by an abdominal midline incision. After bladder instillation with 150 ml NaCl 1 bilateral and 2 unilateral stimulations (left and right sides) were performed and intravesical pressure was recorded urodynamically. The left ureter was then prepared circularly in 3 steps 10, 5 and 1 cm, respectively, proximal to the ureterovesical junction. After each preparation step bilateral and unilateral stimulation was repeated. Results were recorded urodynamically and video documented. RESULTS: Bilateral stimulation before preparation of the left ureter led to a concentric detrusor contraction with an average maximum detrusor pressure of 51 cm H(2)O. Unilateral stimulation resulted in ipsilateralbound bladder tilting with an intravesical pressure of 18 and 19 cm H(2)O on the right and left sides, respectively. After preparation of the left ureter 10, 5 and 1 cm from the ureterovesical junction a maximum detrusor pressure of 17, 10 and 1 cm H(2)O was documented, respectively. While there was almost no stimulation response of the bladder after the last preparation step at 1 cm on the left ureter, the initial bladder pressure of 18 cm H(2)O could be reproduced under stimulation on the right side. CONCLUSIONS: Analogous to human cadaver studies, we were able to prove neurophysiologically strictly unilateral detrusor innervation, drawing from the pelvic plexus dorsomedial to the ureterovesical junction into the bladder. Preparation of this ureterovesical junction during antireflex surgery, coagulating measures in this area or the affixation of anchor sutures after a Vest suture involves the risk of unilateral or bilateral detrusor decentralization.

The role of the carbachol test and concomitant diseases in patients with nonobstructive urinary retention undergoing sacral neuromodulation.

The aim of this study was to evaluate the percutaneous nerve evaluation (PNE) test success in patients with nonobstructive urinary retention. A total of 24 PNE tests were performed in patients with nonobstructive urinary retention and in 18 patients, a carbachol test was performed during urodynamics. The diagnosis relating to the acontractile detrusor was also assessed and compared to the outcome of the PNE test. The PNE test was successful in eight of 24 patients (33.3%) with the the highest success rate being observed in patients after hysterectomy (80%). It was successful in five of 12 patients with negative carbachol tests and in three of six patients with positive carbachol tests. We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. PNE tests should be performed in all patients with therapy resistant nonobstructive urinary retention, because predictive factors do not exist.

Effect of subthalamic deep brain stimulation on the function of the urinary bladder.

Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic deep brain stimulation has a significant and urodynamically recordable effect leading to a normalization of pathologically increased bladder sensibility.