Persistent storage symptoms after TURP can be predicted with a nomogram derived from the ice water test.

PURPOSE: To predict the persistence of storage symptoms after transurethral resection of the prostate (TURP) using a nomogram derived from the ice water test (IWT). METHODS: The IWTs of 73 men with lower urinary tract symptoms and prostatic bladder outlet obstruction were retrospectively analyzed. The strength of the detrusor contraction was approximated by using the detrusor gradient of Δpdet /Δt at maximum detrusor pressure and the area under the curve. The parameters were utilized in a nomogram, which facilitated a severity categorization from 1 to 10. Patients with a positive IWT in the categories 1 to 2 were assigned to group A, categories 3 to 4 to group B and categories 5 and higher to group C. After TURP, patients with persisting storage symptoms were offered a botulinum toxin injection. RESULTS: There were 32 patients (44%) with negative and 41 patients (56%) with positive IWTs. Patients with negative IWTs were classified in category 1. Regarding patients with positive IWTs, 14 (34%) were correlated to group A, 14 (34%) to group B, and 13 (32%) to group C. The necessity of a subsequent botulinum toxin injection correlated significantly with a higher nomogram category (P < .001) as well as higher severity categorization (P < .001). In multivariate analysis, the nomogram category was an independent predictor for botulinum toxin injection (P = .002, OR, 6.9, CI, 2.0-23.9). CONCLUSION: The quantification of the detrusor contraction during the IWT allowed stratification of patients in risk categories for persistent storage symptoms after TURP and the potential need for later botulinum toxin injections.

Ice water test in multiple sclerosis: A pilot trial.

OBJECTIVES: To investigate the significance of the ice water test in patients with multiple sclerosis and to evaluate a novel ice water test nomogram in a large patient cohort. METHODS: A total of 201 ice water tests of patients with multiple sclerosis were retrospectively evaluated. Incontinence episodes in 24 h and sex were correlated with the ice water test. Furthermore, an ice water test nomogram was developed in order to categorize the detrusor overactivity in severity degrees. Descriptive statistics were carried out for population characteristics. Correlations of categorical variables were calculated by the χ2 -test. The independent t-test was carried out for correlations of continuous variables. Furthermore, the data were evaluated in the novel ice water test nomogram. RESULTS: The patient population consisted of 141 (70.1%) women and 60 (39.9%) men. A clinically positive ice water test (maximum detrusor pressure >15 cmH2 O) was identified in 75 patients (37.3%). Significantly more men presented a clinically positive ice water test (P = 0.006). In 16.5%, the ice water test unmasked an involuntary detrusor contraction, although routine cystometry did not show any detrusor overactivity. The ice water test nomogram could be successfully applied. The incontinence episodes and maximum detrusor pressure correlated positively with a higher categorization in the nomogram. Therapeutic interventions and follow-up controls could be successfully illustrated by the nomogram. CONCLUSIONS: The ice water test is a simple tool for unmasking non-identified detrusor overactivity in neurogenic bladder dysfunction. A severity categorization of the detrusor overactivity can be facilitated by the use of the ice water test nomogram. After further validation, the ice water test could be ultimately used in future as objective assessment for bladder dysfunction.

Sensation of Cold during the Ice Water Test Corresponds to the Perception of Pain during Botulinum Toxin Bladder Wall Injections.

AIMS: To investigate the association of bladder cold sensation (BCS) during the ice water test (IWT) and pain perception when botulinum toxin injections (BTI) are administered into the bladder wall. MATERIAL AND METHODS: In 86 patients with idiopathic overactive bladder, the BCS during the IWT was investigated. Patients were divided into 2 groups: with and without BCS. During subsequent administration of BTI, the number of perceived and painful injections as well as the pain levels on a 0-100 pain scale were compared in both groups using Student t test. RESULTS: Thirty-five patients reported a BCS, while 51 did not. After 10 BTI, the mean number of perceived injections was 7.9 in patients with and 2.4 in patients without BCS (p < 0.0001). The mean number of painful injections was 5.4 in patients with BCS and 4.3 in patients without (p < 0.001). Mean levels on a 0-100 pain scale were 33.7 in patients with and 17.8 in patients without cold sensation (p < 0.0001). CONCLUSION: The association of BCS during the IWT and pain to during BTI may implicate that the perceptions of cold and pain in the urinary bladder may use similar receptors and neuronal pathways.

A Nomogram to Characterize the Severity of Detrusor Overactivity during the Ice Water Test: Description of the Method and Proof of Concept.

AIMS: To develop a nomogram with severity categories for detrusor overactivity (DO). METHODS: By conducting ice water tests (IWT) in 55 patients with Parkinson's disease, we identified criteria to describe characteristics of the detrusor pressure curves: (1) a gradient of Δpdet over Δt at the maximum detrusor pressure and (2) the area under the curve. In a nomogram, 10 severity categories of DO were established: 1 and 2 were assigned to group A (mild), 3 and 4 to group B (moderate) and 5-10 to group C (severe). RESULTS: In the nomogram, negative IWT (20) appeared in category 1. Positive IWT (35) spread over the categories 1-8, 17 in group A, 11 in group B and 7 in categories 5-10. A relationship of incontinence episodes and nomogram category was observed. The nomogram category was reproducible in repeated IWT. Therapeutic interventions to treat DO lowered the nomogram category. CONCLUSION: From the relationship of detrusor pressure and time in the IWT, a nomogram with 10 severity categories of DO was developed. First observations show a relationship of nomogram category and the number of incontinence episodes, reproducibility in repeated tests and the representation of effects of therapeutic interventions to treat DO.

[Bipolar stimulation may improve the efficacy of the percutaneous nerve evaluation test of sacral neuromodulation]. / Die bipolare Stimulation kann die Erfolgsrate des Peripheren Nervenevaluationstests der sakralen Neuromodulation verbessern.

Purpose This study evaluates the hypothesis that bipolar stimulation of the S3 and S4 sacral roots may enhance the efficacy of the percutaneous nerve evaluation (PNE) test. Material and Methods In this case-control-study, we enrolled 43 patients undergoing bipolar PNE and 57 controls undergoing unipolar PNE. For bipolar PNE, four test electrodes were placed at the bilateral S3 and S4 roots. The electrodes at the S3 and S4 roots of each side were connected to obtain bipolar stimulation. The test protocol over eight days included unilateral and bilateral stimulation of the S3 and S4 sacral roots. Eight days after implantation, the electrodes were removed and test results from bladder diaries were collected. Results The unipolar test procedure was successful in 47 % (27/57) of cases. The bipolar test procedure was successful in 58 % (25/43). In the bipolar group, 63 % (12/19) of patients with neurogenic tract dysfunction profited from treatment, vs. 57 % (13/23) in the unipolar group. Patients without a neurologic disease had a successful test in 58 % (14/24) of cases treated with bipolar PNE vs. 41 % (14/24) treated with unipolar PNE. Multivariate analysis did not reveal a statistically significant difference between groups. Conclusion Although not significant in this population, bipolar PNE may improve efficacy compared to the unipolar test procedure. Similar observations were made in subgroups of neurogenic and non-neurogenic bladder dysfunctions.

Efficacy, safety, and tolerability of intravesically administered 0.1% oxybutynin hydrochloride solution in adult patients with neurogenic bladder: A randomized, prospective, controlled multi-center trial.

AIMS: To verify the efficacy, safety and tolerability of intravesical administration of 0.1% oxybutynin hydrochloride compared to its oral administration for treatment of neurogenic detrusor overactivity (NDO) in a randomized, prospective, controlled, open-label, multi-center trial in 35 adult patients. METHODS: NDO was confirmed within the previous 24 months by urodynamic studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin hydrochloride orally three times per day for a period of 28 days. Primary efficacy criterion was the change in the maximum bladder capacity between the beginning of the study and after 4 weeks as assessed by UDS. Adverse drug reactions (ADR) were collected and an evaluation of anticholinergic effects was conducted. RESULTS: The increase in maximum bladder capacity was 117 ml with intravesical application (P = 0.0002) versus 18 ml with the oral application (P = 0.51). The difference was statistically significant (P = 0.0086). ADR were reported by 10 (55.6%) of patients with intravesical administration, and by 14 (82.4%) of patients with oral administration. Significant differences in favor of the intravesical application were observed in ADR affecting vision (1/10 vs. 9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14), and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were reported. CONCLUSIONS: This study demonstrates the efficacy and safety of intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect to the increase in maximum bladder capacity. Neurourol. Urodynam. 35:582-588, 2016. © 2015 Wiley Periodicals, Inc.

Midterm results of robot-assisted sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Robotic assistance simplifies laparoscopic procedures. We hypothesize that robot-assisted sacrocolpopexy is a rapid and safe procedure with satisfying short-term and midterm functional results. METHODS: After informed consent, we enrolled 101 consecutive patients undergoing sacrocolpopexy at Alfried Krupp Hospital, Essen, Germany. After a median follow-up of 22 months, we assessed midterm functional results as the primary endpoint. Secondary endpoints included surgical duration, blood loss, intraoperative complications, and postoperative complications. We described frequencies as counts (percent) and continuous data as median [interquartile range (Q1-Q3)] or mean [standard deviation (SD)], as appropriate. RESULTS: We enrolled 101 patients. The mean age was 69 years (SD 11); 75 women (74.3 %) had undergone previous abdominal surgery. Among the patients, 95 (94.1 %) presented with anterior vaginal wall prolapse Baden-Walker grade 2-3, 74 (73.3 %) vaginal vault prolapse, and 9 (8.9 %) concomitant rectocele. Fifty (50 %) patients underwent a modified Burch procedure in addition to sacrocolpopexy. The median surgical duration was 96 min (Q1-Q3 83-130). There were six (5.9 %) minor intraoperative complications but no conversions to open surgery. Postoperatively, we registered five (4.9 %) Clavien-Dindo grade I complications, three (3.0 %) grade II complications, and one (1.0 %) grade III complication. After a median follow-up of 22 months (Q1-Q3 12-49), the patients reported significant decreased impact of pelvic organ prolapse (POP) on quality of life as well as bother resulting from POP symptoms. The overall success rate, defined as none or minor impact of POP on quality of life, was 75 %. CONCLUSIONS: In this single-surgeon study, robot-assisted sacrocolpopexy was a safe and rapidly performed procedure that achieved good medium-term functional results.

Lower urinary tract dysfunction in critical illness polyneuropathy.

BACKGROUND: Critical illness polyneuropathy is a frequent complication of critical illness in intensive care units. Reports on autonomic systems like lower urinary tract and bowel functions in patients with CIP are not available in medical literature. OBJECTIVE: This study performed during primary rehabilitation of patients with critical illness polyneuropathy explores if sensory and motor pathways controlling the lower urinary tract function are affected from the disease. METHODS: Neurourological examinations, urodynamics, electromyography and lower urinary tract imaging were performed in 28 patients with critical illness polyneuropathy. DISCUSSION: Sacral sensation was impaired in 1 patient (4%). Sacral reflexes were absent in 8 patients (30%). Anal sphincter resting tone was reduced in 3 (12%), anal sphincter voluntary contraction was absent or reduced in 8 patients (30%). Urodynamic findings were detrusor overactivity and detrusor overactivity incontinence in 9 (37.5%), incomplete voiding in 8 (30%), abnormal sphincter activity in 4 (16%), abnormal bladder sensation in 4 (16%) and detrusor acontractility in 2 patients (8.3%). Morphological abnormalities of the lower urinary tract had 10 patients (41.6%). CONCLUSION: Sensory and motor pathways controlling the lower urinary tract might be affected from CIP. During urodynamics dysfunctions of the storage as well as the voiding phase were found. Morphological lower urinary tract abnormalities were common.

Afferent pathways arising from the lower urinary tract after complete spinal cord injury or cauda equina lesion: clinical observations with neurophysiological implications.

BACKGROUND: Afferents from the urinary tract transmit bladder sensations to the central nervous system. Spinal cord injury (SCI) may affect both efferent motor and afferent sensory pathways. Presence/absence of bladder sensations in patients with complete spinal cord, conus or cauda equina lesions was compared with neurologically unimpaired patients. METHODS: During urodynamics, bladder sensations were studied and compared in 59 patients: 21 patients with complete SCI below T6 and above Th12, 7 patients with a complete lesion of the conus medullaris, 11 patients with a complete lesion of the cauda equina, and 20 patients without neurological deficit. RESULTS: Two of 7 patients with complete conus lesion had a preserved filling sensation. Ten of 11 patients with complete lesion of the cauda equina reported a bladder filling sensation. Sensations are perceived at a similar pressure threshold but at a higher volume threshold. CONCLUSIONS: In patients with a complete cauda or a lower conus lesion, a sensory input from the bladder is preserved. These findings imply that the preserved bladder filling sensation in complete cauda or lower conus lesions is possibly transferred through the intact hypogastric plexus to the thoracolumbar segments of the spinal cord.

Proof of principle: The effect of antimuscarinics on bladder filling sensations in healthy subjects--a placebo controlled double blind investigation using 4 and 8 mg tolterodine extended release.

AIMS: There is evidence that antimuscarinic drugs have depressant influence not only on bladder muscle activity, but also on bladder sensations. The aim of this study was to evaluate the effect of a single dose tolterodine extended release (ER) 4 and 8 mg on bladder sensations during filling cystometry. METHODS: After approval of the local ethics committee, 30 healthy female subjects (23.7 +/- 2.3 years) were included and randomly assigned to three groups: (A) placebo, (B) tolterodine ER 4 mg, and (C) tolterodine ER 8 mg in a double blind manner. Measurements were performed at baseline and 4 hr postmedication in each group, consisting of: (1) Filling cystometry with 25 ml/min at which subjects had to indicate first sensation of filling (FSF), first desire to void (FDV), and strong desire to void (SDV). (2) Uroflowmetry and ultrasound control for residual urine. RESULTS: In the placebo group, filling volumes at FDV and SDV decreased significantly posttreatment. This effect could not be observed for the tolterodine 8 mg group and only at SDV in the 4 mg group. No significant difference between groups was found regarding uroflowmetry parameters and postvoid residual volume. CONCLUSIONS: No increase of filling volumes in healthy subjects could be observed with tolterodine. However, the results suggest that tolterodine is able to alleviate irritation caused by repeated catheterization and cystometry. There was no significant influence of tolterodine ER 4 or 8 mg on voiding function.

The facilitatory effect of duloxetine combined with pelvic floor muscle training on the excitability of urethral sphincter motor neurons.

INTRODUCTION AND HYPOTHESIS: Aim of this study was to investigate the excitability of sphincter motor neurons under the influence of pelvic floor muscle training (PFMT) and duloxetine. Due to their mechanisms of action, there might be a synergistic effect of duloxetine and PFMT in regard to the facilitation of spinal reflexes controlling urethral sphincter contractions and hence continence. METHODS: In ten healthy female subjects, clitoral electric stimulation (CES) and transcranial magnetic stimulation (TMS) were used to determine individual motor thresholds for external urethral sphincter (EUS) contractions before and after PFMT, duloxetine, and PFMT + duloxetine. RESULTS: PFMT and duloxetine alone significantly decreased the motor thresholds for EUS contractions during CES and TMS. However, the combined treatment reduced the motor threshold for EUS contractions significantly stronger compared to PFMT or duloxetine alone. CONCLUSIONS: The results are suggestive for a synergistic facilitatory effect of PFMT and duloxetine on sphincter motor neuron activation.

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging.

OBJECTIVES: Although botulinum neurotoxin type A (BoNT/A) intradetrusor injections are a recommended therapy for neurogenic detrusor overactivity (NDO), refractory to antimuscarinic drugs, a standardisation of injection technique is missing. Furthermore, some basic questions are still unanswered, as where the toxin solution exactly spreads after injection. Therefore, we investigated the distribution of the toxin solution after injection into the bladder wall, using magnet resonance imaging (MRI). METHODS: Six patients with NDO were recruited. Three of six patients received 300 U of BoNT/A + contrast agent distributed over 30 injection sites (group 1). The other three patients received 300 U of BoNT/A + contrast agent distributed over 10 injection sites (group 2). Immediately after injection, MRI of the pelvis was performed. The volume of the detrusor and the total volume of contrast medium inside and outside the bladder wall were calculated. RESULTS: In all patients, a small volume (mean 17.6%) was found at the lateral aspects of the bladder dome in the extraperitoneal fat tissue, whereas 82.4% of the injected volume reached the target area (detrusor). In both groups there was a similar distribution of the contrast medium in the target area. A mean of 33.3 and 25.3% of the total detrusor volume was covered in group 1 and 2, respectively. Six weeks after injection, five of six patients were continent and showed no detrusor overactivity in the urodynamic follow-up. No systemic side effects were observed. CONCLUSIONS: Our results provide morphological arguments that the currently used injection techniques are appropriate and safe.

Heart rate variability: an objective measure of autonomic activity and bladder sensations during urodynamics.

AIMS: There are still controversies regarding the reproducibility of cystometric data and no objective measurement of bladder sensations is currently available. Additionally, very little information exists about autonomic activity during standard filling cystometry (FC). The aim of this study was to evaluate the use of heart rate variability (HRV) analysis as a reliable monitor of the autonomic nervous system and objective measure for bladder sensations during FC. METHODS: In a volunteer sample of healthy female subjects a standard FC at 25 ml/min was performed, using an 8 Fr microtip catheter with integrated pressure transducers. During FC, subjects had to indicate first sensation of filling (FSF), first desire to void (FDV) and strong desire to void (SDV). A 3-lead electrocardiogram was continuously recorded. After 5 h all measurements were repeated. Power spectrum analysis was used to analyse HRV, to obtain low frequency (LF) and high frequency (HF) parameters, from which the LF/HF ratio was derived. RESULTS: 12 subjects with a mean age of 23.3 +/- 2.3 years could be included. 11 of 12 subjects completed both measurement sessions. One subjects had to be excluded, due to irritating urethral discomfort following catheterisation. The LF/HF ratio showed a reproducible activation pattern in the healthy subjects with a stable sympathovagal balance until FDV. Before SDV was indicated, the sympathovagal balance started to shift towards sympathetic activation and caused a significant increase in LF/HF. CONCLUSION: HRV analysis seems to be a useful indicator for the general activation pattern of the sympathovagal balance during FC, correlating the intensity of the bladder filling sensation to stress and sympathetic activation.

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve--an fMRI study in healthy women.

AIMS: Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS: After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS: A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION: Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.

Does tolterodine extended release affect the bladder electrical perception threshold? A placebo controlled, double-blind study with 4 and 8 mg in healthy volunteers.

PURPOSE: We evaluated the influence of tolterodine extended release on human bladder afferents. The afferents were assessed by determining the bladder electrical perception threshold using endovesical electrical stimulation at different potentially neuroselective frequencies. MATERIALS AND METHODS: A total of 30 healthy female subjects with a mean +/- SD age of 23.6 +/- 2.3 years and a mean body mass index of 20.5 +/- 1.7 kg/m2 were assigned to 3 groups of 10 each in a double-blind manner, including group 1-placebo, group 2-4 mg tolterodine extended release and group 3-8 mg tolterodine extended release. The investigation was performed using an 8Fr catheter for filling and stimulation that was placed at the bladder neck in a 100 ml filled bladder. Bipolar stimulation was performed using 2.5, 5 and 250 Hz stimuli. Subjects were asked to indicate sensation by pressing a button. Electrical perception thresholds were determined using the method of levels. Electrical perception thresholds were determined before and 4 hours after medication. RESULTS: No significant change in the electrical perception threshold after treatment could be found among the groups at 2.5, 5 and 250 Hz (p = 0.178, 0.817 and 0.365, respectively). There was a tendency in the tolterodine extended release groups toward an increased electrical perception threshold at 250 Hz (4 mg less than 8 mg). In most cases electrical stimulation with 2.5 and 5 Hz was described as a slight twinge, tickle or desire to void. Stimulation with 250 Hz was the most uncomfortable one, described as a strong, distinct twinge or burning "like urinary tract infection." CONCLUSIONS: Although a tendency was observed toward an increased electrical perception threshold at 250 Hz, this study showed no significant effect of tolterodine extended release on the bladder electrical perception threshold.

Do repeat intradetrusor botulinum toxin type a injections yield valuable results? Clinical and urodynamic results after five injections in patients with neurogenic detrusor overactivity.

OBJECTIVES: To study repeat intradetrusor botulinum toxin injections for the treatment of neurogenic detrusor overactivity in terms of safety and improvement of continence status and urodynamic parameters. MATERIAL AND METHODS: This study was based on 20 consecutive patients (13 males, 7 females; median age, 41.1 yr) who received at least five intradetrusor injections of botulinum toxin and who were followed by clinical and urodynamic evaluation after at least four injections. The results of 100 injections and corresponding follow-ups were analyzed and compared with baseline. RESULTS: No toxin-related side effects were observed after the first or repeat injections. All patients had a baseline urodynamic study and at least four urodynamic studies after botulinum toxin injections. Clinical continence improved significantly after the first injection and then remained constant after repeat injections. The median reflex volume increased significantly from a median of 200 ml at baseline to values between 440 and 500 ml at follow-up studies. The presence of neurogenic detrusor overactivity decreased significantly by 60-75%. Maximum cystometric capacity increased significantly 2.3-fold. Maximum detrusor pressure during cystometry decreased significantly 5.8-fold from a median of 70 cm H(2)O to values of about 20 cm H(2)O. Median compliance at baseline (60 ml/cm H(2)O) did not change significantly. CONCLUSION: Repeat intradetrusor botulinum toxin A injections are a safe and valuable treatment option for neurogenic detrusor overactivity over a period of several years. The beneficial effect of the toxin on clinical and urodynamic parameters remains constant after repeat injections.