Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder.

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

Effect duration of the initial course of peroneal electrical Transcutaneous NeuroModulation in patients with overactive bladder.

PURPOSE: The aim of this prospective 12-month follow-up study is to evaluate the persistence of the treatment effect achieved during the initial course of peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) in patients with overactive bladder (OAB). METHODS: This study enrolled 21 female patients who participated in two previous clinical studies designed to assess the efficacy and safety of peroneal eTNM®. The patients were left without subsequent OAB treatment and were invited to attend regular follow-up visits every 3 months. The patient's request for additional treatment was considered an indicator of the withdrawal of the treatment effect of the initial course of peroneal eTNM®. The primary objective was the proportion of patients with persisting treatment effect at follow-up visit 12 months after initial course of peroneal eTNM®. Descriptive statistics are presented using median, correlation analyses were computed using a nonparametric Spearman correlation. RESULTS: The proportion of patients with persistent therapeutic effect of the initial course of peroneal eTNM® was 76%, 76%, 62% and 48% at 3, 6, 9 and 12 months, respectively. There was a significant correlation between patient reported outcomes and the number of severe urgency episodes with or without urgency incontinence as reported by patients at each follow-up visit (p = 0.0017). CONCLUSION: The treatment effect achieved during the initial phase of peroneal eTNM® persists for at least 12 months in 48% of patients. It is likely that the duration of effects is dependent on the length of the initial therapy.

Differences between brain responses to peroneal electrical transcutaneous neuromodulation and transcutaneous tibial nerve stimulation, two treatments for overactive bladder.

OBJECTIVES: To compare brain responses to peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) and transcutaneous tibial nerve stimulation (TTNS), two methods for treating overactive bladder (OAB), using functional magnetic resonance imaging (fMRI). The present study was not designed to compare their clinical efficacy. MATERIALS AND METHODS: This study included 32 healthy adult female volunteers (average age 38.3 years (range 22-73)). Brain MRI using 3 T scanner was performed during three 8-min blocks of alternating sequences. During each 8-min block, the protocol alternated between sham stimulation (30 s) and rest (30 s) for 8 repeats; then peroneal eTNM® stimulation (30 s) and rest (30 s) for 8 repeats; then, TTNS stimulation (30 s) and rest (30 s) for 8 repeats. Statistical analysis was performed at the individual level with a threshold of p = 0.05, family-wise error (FWE)-corrected. The resulting individual statistical maps were analyzed in group statistics using a one-sample t-test, p = 0.05 threshold, false discovery rate (FDR)-corrected. RESULTS: During peroneal eTNM®, TTNS, and sham stimulations, we recorded activation in the brainstem, bilateral posterior insula, bilateral precentral gyrus, bilateral postcentral gyrus, left transverse temporal gyrus, and right supramarginal gyrus. During both peroneal eTNM® and TTNS stimulations, but not sham stimulations, we recorded activation in the left cerebellum, right transverse temporal gyrus, right middle frontal gyrus, and right inferior frontal gyrus. Exclusively during peroneal eTNM® stimulation, we observed activation in the right cerebellum, right thalamus, bilateral basal ganglia, bilateral cingulate gyrus, right anterior insula, right central operculum, bilateral supplementary motor cortex, bilateral superior temporal gyrus, and left inferior frontal gyrus. CONCLUSIONS: Peroneal eTNM®, but not TTNS, induces the activation of brain structures that were previously implicated in neural control of the of bladder filling and play an important role in the ability to cope with urgency. The therapeutic effect of peroneal eTNM® could be exerted, at least in part, at the supraspinal level of neural control.

Peroneal electrical transcutaneous neuromodulation in the home treatment of the refractory overactive bladder.

INTRODUCTION AND HYPOTHESIS: The aim of this prospective, open-label, multicenter, noncomparative study was to evaluate the efficacy and safety of peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) using the URIS® neuromodulation system as a home treatment for refractory overactive bladder (OAB). METHODS: The patients were treated with daily peroneal eTNM® for 30 min over a 6-week period. The primary endpoint was defined as the proportion of responders, i.e., participants with ≥ 50% reduction in the average daily sum of severe urgency episodes (defined as "I could not postpone voiding but had to rush to the toilet in order not to wet myself") and urgency incontinence episodes. In addition, bladder diary variables, symptom severity (OAB V8 questionnaire), treatment satisfaction (visual analog scale), and pain perception (visual analog scale) were evaluated at baseline (BL), at week 4 (W4), and at the end of treatment (EoT). Safety evaluations included monitoring of the incidence and severity of adverse events (AEs). Changes in time were analyzed using the nonparametric one-way ANOVA Friedman test for categorical variables and the Wilcoxon rank-sum test for the noncategorical variables. RESULTS: In total, 40 subjects were screened and 29 were included in the full analysis set. The proportion of responders was 86% at W4 and 79% at EoT. There was a significant reduction in frequency (p<0.001), number of severe urgency episodes (p< 0.001), number of urgency incontinence episodes (p=0.001), and number of nocturia episodes (p=0.002). There was a significant improvement in the OAB V8 score and treatment satisfaction (both p<0.001). Two mild treatment-related AEs were recorded. Both patients recovered without sequelae and completed the study. CONCLUSIONS: Peroneal eTNM® proved to be a highly effective and safe method for the home treatment of OAB, providing a therapeutic response in approximately 80% of patients.

Peroneal Electrical Transcutaneous NeuroModulation as a New Treatment for Patients with Overactive Bladder: An Initial Clinical Experience.

INTRODUCTION: The aim of this study was to determine whether peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) using the URIS® neuromodulation system can be used in individuals with refractory overactive bladder (OAB). METHODS: Eighteen female patients with idiopathic OAB who failed previous behavioral and pharmacological therapy were enrolled. Patients were treated with the URIS® neuromodulation system using active electrodes placed on the popliteal fossa, targeting the peroneal nerve for 30 min once a week for 12 weeks. Changes in OAB symptoms and patient-reported outcomes from baseline to the end of the study were analyzed. A nonparametric Wilcoxon signed-rank test was used to assess changes in variables. Statistical significance was defined as p ≤ 0.05. RESULTS: We observed a significant reduction in micturition frequency (p = 0.022), number of severe urgency episodes (p < 0.001), urgency incontinence episodes (p = 0.001), and nocturia episodes (p = 0.027). A decrease in Patient Perception of Bladder Condition score (p < 0.001) was also observed. Posttreatment, 15 patients (83.3%) reported a moderate or significant reduction in their bladder bother. Throughout the study, two adverse events were recorded with no causal relationship to the study treatment. DISCUSSION/CONCLUSIONS: Our study documented a significant reduction in all OAB symptoms and an improvement in all patient-reported outcomes in patients treated with peroneal eTNM® using the URIS® neuromodulation system.

ICS Educational Module: Electromyography in the assessment and therapy of lower urinary tract dysfunction in adults.

AIM: To present the teaching module "Electromyography in the assessment and therapy of lower urinary tract dysfunction in adults." This teaching module embodies a presentation, in combination with this manuscript. This manuscript serves as a scientific background review; the evidence base made available on ICS website to summarize current knowledge and recommendations. METHODS: This review has been prepared by a Working Group of The ICS Urodynamics Committee. The methodology used included comprehensive literature review, consensus formation by the members of the Working Group, and review by members of the ICS Urodynamics Committee core panel. RESULTS: Electromyography (EMG) is a method to record spontaneous or artificially induced electrical activity of the nerve-muscle unit or to test nerve conductivity. EMG of the anal sphincter using surface electrode is most widely used screening technique to detect detrusor-sphincter dyssynergia in urology. It is non-invasive and easy to perform. EMG methods using needle electrodes are reserved for diagnostics in well selected group of mainly neurogenic patients. These methods require expertise in the field of general EMG and are usually performed by neurologist and neuro-physiologist. The evidence in many aspects of use of EMG in urology remains sparse. CONCLUSIONS: Currently EMG methods rarely play a decision making role in selecting proper treatment of lower urinary tract dysfunction. With the current efforts to improve phenotyping of these patients in order to provide individualized treatment, the role of EMG could increase.

Effect of severity of urinary incontinence on quality of life in women.

AIMS: While the effect of different types of incontinence on the quality of life (QoL) has been clearly documented, the information about the impact of incontinence severity on QoL in women is lacking. Therefore, we investigated whether increasingly severe degrees of incontinence were linearly correlated with poorer QoL. METHODS: We included 391 incontinent women and 81 continent volunteers in the study and assessed them in accordance with routine clinical practice. A 24 h pad-weight test was used to objectively quantify the incontinence severity. We then stratified participants according to incontinence type and severity and assessed correlations between incontinence severity and Patient Perception of Bladder Condition (PPBC), International Consultation on Incontinence short-form questionnaire (ICIQ-SF), and King's Health Questionnaire (KHQ) quality of life scores in the entire study population and in individual groups according to incontinence type. RESULTS: Minimal incontinence was associated with significant negative impact on QoL, as measured by all quality of life assement tools. There were nonlinear correlations between scores on individual questionnaires and daily leakage volumes. Stress urinary incontinence had a weaker impact on quality of life than urge or mixed incontinence, as measured by PPBC (P < 0.0001), KHQ part 1 (P < 0.0001), and KHQ part 2 (P < 0.001). Stress urinary incontinence also had a weaker impact on QoL than mixed incontinence as measured by ICI-Q (P = 0.007). CONCLUSIONS: This study demonstrated that even mild urinary leakage significantly reduces the QoL, while subsequent increase in the degree of incontinence has only minimal additional effect. There was no linear correlation between incontinence severity and QoL.

Evaluation of intra-individual test-re-test variability of uroflowmetry in healthy women and women suffering from stress, urge, and mixed urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the intra-individual variability of uroflowmetry (UFM) in healthy control subjects and women suffering from stress, urge, and mixed urinary incontinence. METHODS: A total of 35 healthy controls (group A) and 105 women suffering from urinary incontinence were enrolled in the study. Thirty-five women suffered from stress urinary incontinence (group B), 35 women suffered from mixed urinary incontinence (group C), and 35 women with overactive bladder both dry and wet (group D). All participants were asked to perform UFM measurement three times. The following parameters were analyzed: voided volume (VV), peak flow (Qmax), average flow (Qave), volume-corrected peak flow cQmax (cQmax = Qmax/2√ VV), volume-corrected average flow (cQave = Qave/2√ VV), and postvoid residual volume (PVR). Statistical analysis was performed using the analysis of variance on repeated measurements. Relative error was calculated using variation coefficients reported as a percentage of the average. All descriptive characteristics were reported as means ± standard deviation (SD). p values ≤0.05 were considered statistically significant. RESULTS: No statistically significant intra-individual difference in any of the recorded parameters was identified among the three UFM recordings in groups A, C, and D. The intra-individual variability of the following parameters reached statistical significance in patients suffering from stress urinary incontinence (group B): Qmax (p = 0.0016), Qave (p = 0.0005), and cQave (p = 0.0389). A significant difference was only observed in comparison between the first and second consecutive recordings. CONCLUSIONS: This study provides evidence supporting the high yield and good intra-individual reproducibility of UFM.

Brain activity on fMRI associated with urinary bladder filling in patients with a complete spinal cord injury.

OBJECTIVE: Patients with complete spinal cord injury (SCI) may maintain some perception of bladder fullness. The aim of the study was to evaluate brain activation arising from anticipated extraspinal sensory pathways. METHODS: Fourteen patients ages 24-54 years were enrolled, all having experienced a complete SCI (ASIA A) at C7 to T5 an average of 17 months before study entry. Urodynamic equipment was used for repeated bladder filling and detrusor activity evaluation. All functional magnetic resonance imaging measurements were performed using a Siemens Trio 3T scanner with the GRE-EPI sequence (field of view = 192 × 192 mm, voxel 3 × 3 × 3 mm, TR/TE = 3000/30 ms, 45 slices). Nine hundred dynamic scans were acquired over 45 min. Statistical analysis was done in SPM8 using a general linear model. Statistics using t-tests were thresholded at P = 0.001. RESULTS: We excluded results from two patients because of activation artifacts. In 8 of 12 patients, significant brain activity was observed during urinary bladder filling. We found significant activation clusters at the nucleus of the solitary tract (NTS) (3/8), parabrachial nucleus (PBN) (4/8), hypothalamus (4/8), thalamus (6/8), amygdala (7/8), insular lobe (5/8), anterior cingulate gyrus (5/8), and prefrontal cortex (8/8). Activations in nuclei involved in afferents likely from the vagal nerve (NTS and PBN) correlated significantly with reported bladder sensations. CONCLUSIONS: These data suggest that extraspinal sensory pathways may develop following SCI and that vagal nerve may play a role in re-innervation of the urinary bladder. Neurourol. Urodynam. 36:155-159, 2017. © 2015 Wiley Periodicals, Inc.

Treatment of stress urinary incontinence using polyacrylamide hydrogel in women after radiotherapy: 1-year follow-up.

INTRODUCTION AND HYPOTHESIS: Information on urethral bulking therapy in women after previous pelvic radiotherapy is lacking. This study compared the safety and efficacy of polyacrylamide intraurethral injections in patients with and without previous radiotherapy. METHODS: A total of 46 patients with severe stress urinary incontinence (SUI) were enrolled in this multicenter prospective trial. Group A consisted of 24 patients with previous radiotherapy to the pelvis for the treatment of a gynaecological malignancy. Group B consisted of 22 patients without previous radiotherapy. All patients were treated with a transurethral injection of a bulking solution (Bulkamid). The average follow-up was 12.4 months. The paired Wilcoxon test was used to compare the results before and after the procedure within the groups, and the two-sample Wilcoxon test was used for comparisons between groups. RESULTS: Complete continence was achieved in 25 % of patients in group A and in 36.4 % of patients in group B. Significantly reduced urine leakage was observed in both groups (p = 0.0164 in group A and p = 0.0002 in group B). The total scores in the International Consultation on Incontinence Questionnaire decreased by 5.2 in group A (p = 0.0000) and 6.36 in group B (p = 0.0001). The scores for the Total Patient Perception of Bladder Condition decreased by 1.54 in group A (p = 0.0001) and 2.59 in group B (p = 0.0000), with a significant difference between groups (p = 0.0224). No clinically significant changes in urodynamic parameters were observed. No severe adverse events were noted. CONCLUSIONS: Based on our results, we conclude that urethral bulking therapy is a valuable treatment option in patients with severe SUI who have undergone pelvic radiotherapy for the treatment of gynaecological malignancy.

Comparison between uroflowmetry and sonouroflowmetry in recording of urinary flow in healthy men.

OBJECTIVES: To evaluate the accuracy of sonouroflowmetry in recording urinary flow parameters and voided volume. METHODS: A total of 25 healthy male volunteers (age 18-63 years) were included in the study. All participants were asked to carry out uroflowmetry synchronous with recording of the sound generated by the urine stream hitting the water level in the urine collection receptacle, using a dedicated cell phone. From 188 recordings, 34 were excluded, because of voided volume <150 mL or technical problems during recording. Sonouroflowmetry recording was visualized in a form of a trace, representing sound intensity over time. Subsequently, the matching datasets of uroflowmetry and sonouroflowmetry were compared with respect to flow time, voided volume, maximum flow rate and average flow rate. Pearson's correlation coefficient was used to compare parameters recorded by uroflowmetry with those calculated based on sonouroflowmetry recordings. RESULTS: The flow pattern recorded by sonouroflowmetry showed a good correlation with the uroflowmetry trace. A strong correlation (Pearson's correlation coefficient 0.87) was documented between uroflowmetry-recorded flow time and duration of the sound signal recorded with sonouroflowmetry. A moderate correlation was observed in voided volume (Pearson's correlation coefficient 0.68) and average flow rate (Pearson's correlation coefficient 0.57). A weak correlation (Pearson's correlation coefficient 0.38) between maximum flow rate recorded using uroflowmetry and sonouroflowmetry-recorded peak sound intensity was documented. CONCLUSIONS: The present study shows that the basic concept utilizing sound analysis for estimation of urinary flow parameters and voided volume is valid. However, further development of this technology and standardization of recording algorithm are required.

Rat animal model for preclinical testing of microparticle urethral bulking agents.

OBJECTIVES: To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. METHODS: Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. RESULTS: Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. CONCLUSIONS: The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.

Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury (TBI) in rats.

AIMS: The aim of this study was to assess experimental traumatic brain injury (TBI)-induced lower urinary tract dysfunction (LUTD) by monitoring systemic and urodynamic parameters using an implantable telemetry system. METHODS: A single lateral fluid percussion TBI (FP-TBI; 3.4 atm) was administered to 10 female rats. Pressure micro-catheters were implanted in the abdominal aorta and bladder dome for simultaneous data recording. Hemodynamic and urodynamic variables recorded 24 hr before and 24 hr after injury were analyzed and compared. RESULTS: TBI in the acute phase resulted in LUTD affecting bladder emptying, characterized by failure of voiding reflex, high capacity bladder, increased voided volume, prolonged intermicturition intervals, and loss of compliance. The dominant symptom was urinary retention (100%) and incontinence (60%). The effects followed a pattern of initial loss of bladder function followed by either altered recovery of reflex micturition or a period of incontinence. With a moderate injury symptoms were temporary in 90% of animals and permanent in 10% of animals. Injury produced only transient hypertension (≤1 hr) with a maximum systolic pressure of 172.64 ± 14.53 mmHg (70% of animals). CONCLUSIONS: The results demonstrate that experimental FP-TBI causes temporary bladder dysfunction that in more severe cases becomes permanent. Telemetry recordings revealed a sequence of events following injury that establishes moderate TBI as a risk factor for neurogenic bladder disorder. Results also suggest a correlation between lateral FP-TBI and incontinence.

Pad weight testing in the evaluation of urinary incontinence.

AIM: To present the teaching module "Pad Weight Testing in the Evaluation of Urinary Incontinence." This teaching module embodies a presentation, in combination with this manuscript. This manuscript serves as a scientific background review; the evidence base made available on ICS website to summarize current knowledge and recommendations. METHODS: This review has been prepared by a Working Group of The ICS Urodynamics Committee. The methodology used included comprehensive literature review, consensus formation by the members of the Working Group, and review by members of the ICS Urodynamics Committee core panel. RESULTS: The pad test is a non-invasive diagnostic tool for urinary incontinence. It is an easy to perform, inexpensive test with utilization in both the daily patient care and clinical research. Despite it is clear value in initial diagnosis, selection of treatment, and follow-up evaluation, only less than 10% of urologists perform the test routinely. A number of testing protocols with varying lengths of recording time exist, however, only a 1-hr pad test has been standardized. One-hour pad tests are most suitable in establishing initial diagnosis, the 24-hr test serves most often for evaluation of treatment outcomes, and longer pad tests are used in clinical studies. CONCLUSIONS: The pad test is clearly underutilized. Well-designed studies providing level one evidence are lacking. Numerous variations in how the test is performed by individual urologists make the evaluation of published literature difficult. Future research goals should include randomized studies leading to establishment of optimal protocols of testing for clinical research and daily care.

Brain activity during bladder filling and pelvic floor muscle contractions: a study using functional magnetic resonance imaging and synchronous urodynamics.

OBJECTIVES: To map the brain activity during bladder filling by functional magnetic resonance imaging using a refined scanning protocol including synchronous urodynamics and pelvic floor muscle contractions. METHODS: A total of 23 healthy female volunteers (age 20-68 years) were enrolled. Participants were asked to contract their pelvic floor muscles. This was followed by a urodynamic examination consisting of repeated filling cycles. Brain activity was measured by functional magnetic resonance imaging using a 3T magnetic resonance system. Measurements of brain activity consisted of 120 functional scans during pelvic floor contractions and 210 scans during bladder filling. Each functional magnetic resonance imaging scan covered the brain with 35 slices. Statistical analyses used the general linear model and independent component analysis. Areas of activation were visualized using group statistics. RESULTS: The following main clusters of activation were observed during pelvic floor muscle contractions: medial surface of the frontal lobe (primary motor area), bilaterally; supplementary motor area, bilaterally; and left gyrus precentralis. During bladder filling, activation was detected in the inferior frontal lobe bordering the frontal cingulum, left gyrus parietalis superior, left central area, right insula, brainstem and thalamus with subcortical gray matter nuclei. CONCLUSIONS: Our work extends an existing functional magnetic resonance imaging protocol for researching the neural control of the lower urinary tract. The present results are consistent with the available literature and agree with the present hypothetical functional model of lower urinary tract neural control.

Urinary bladder function in conscious rat pups: a developmental study.

Cystometric studies of bladder function in anesthetized neonatal rats have suggested specific changes in urodynamic parameters that coincide with the development of a mature bladder-to-bladder micturition reflex. Here, we used a conscious cystometry model that avoids the potentially confounding effects of anesthesia to characterize voiding patterns and urodynamic parameters during early postnatal development in healthy rat pups. Cystometry was performed on postnatal day (P)0, 3, 7, 14, and 21 rats with continuous intravesical instillation of NaCl via a bladder catheter. Micturition cycles were analyzed with respect to voiding pattern, nonvoiding contractions, infused volume, and basal, filling, threshold, and micturition pressures. Reproducible micturition patterns were obtained from all age groups. The time from stimulation to contraction was significantly longer (P ≤ 0.001) in ≤1-wk-old rats (∼10 s) than that in older rats (∼3 s). An interrupted voiding pattern was observed in ≤10-day-old subgroups. Micturition pressure progressively increased with age (from 21.77 ± 1.92 cmH(2)O at P0 to 35.47 ± 1.28 cmH(2)O at P21, P ≤ 0.001), as did bladder capacity. Nonvoiding contractions were prominent in the P3 age group (amplitude: 4.6 ± 1.3 cmH(2)O, frequency: ∼4.0 events/100 s). At P7, the pattern of spontaneous contractions became altered, acquiring a volume-related character that persisted in a less prominent manner through P21. Bladder compliance increased with age, i.e., maturation. In conclusion, conscious cystometry in rat pups resulted in reproducible micturition cycles that yielded consistent data. Our results revealed immature voiding and prolonged micturition contractions during the first 10 neonatal days and provide evidence for age-related changes in urodynamic parameters.

A preliminary report on the use of functional magnetic resonance imaging with simultaneous urodynamics to record brain activity during micturition.

PURPOSE: We mapped brain activity during micturition using functional magnetic resonance imaging with simultaneous recording of urodynamic properties during slow bladder filling and micturition. MATERIALS AND METHODS: We evaluated 12 healthy female volunteers 20 to 68 years old. Eight subjects could urinate while supine. Meaningful data were obtained on 6 of these subjects. Brain activity was recorded continuously during bladder filling and micturition. Functional magnetic resonance imaging measurements made during the micturition phase were used for the final analysis. RESULTS: Using group statistics we identified clusters of brain activity in the parahippocampal gyrus, anterior cingulate gyrus, inferior temporal gyrus and inferior frontal gyrus during micturition. At the individual level we also observed activation in the upper pontine region, thalamus and posterior cingulum. In subjects unable to void brain activation was documented in the frontal lobe and posterior cingulate gyrus but not in the pons, thalamus or anterior cingulate gyrus. In 5 subjects we identified a relevant pattern of brain activity during the terminal portion of the filling phase when the patient reported a strong desire to urinate. CONCLUSIONS: This new protocol allows for the localization of brain structures that are active during micturition. Data suggest that additional validation studies are needed. Future studies will test modifications that include more detailed monitoring of bladder sensation, stratifying subjects based on age and gender, and increasing the number of data points by adding subjects and the number of micturitions recorded in a single subject.

Caffeine ingestion causes detrusor overactivity and afferent nerve excitation in mice.

PURPOSE: We examined the effect of caffeine (Sigma®) on voiding patterns in mice and characterized potential changes in bladder function and sensory signaling. MATERIALS AND METHODS: A total of 12 mice were fed high dose (150 mg/kg) caffeine daily for 2 weeks. Micturition frequency and volume were recorded at baseline and at the end point. The effects of chronic low dose (10 mg/kg) caffeine on voiding patterns were examined in 7 mice, which were subsequently studied using awake cystometry. In a separate study to characterize the effects of acute caffeine consumption on bladder function and sensory signaling cystometry was performed in 6 mice. Bladder extracellular multifiber afferent signaling was recorded at baseline and 1 hour after feeding low dose caffeine. In a separate group of mice baseline cystometrograms were done using normal saline, followed by a caffeine filling solution. RESULTS: Compared to pretreatment conditions, daily oral high dose caffeine resulted in a significant increase in average micturition frequency and a decreased average volume per void. In animals fed low dose caffeine cystometry demonstrated a statistically significant increase in filling and threshold bladder pressure compared to caffeine naïve animals. Acute low dose caffeine ingestion resulted in a significant increase in filling pressure, an increased frequency of nonvoiding bladder contractions, a decrease in cystometric capacity and a 7.2-fold increase in the average firing rate of afferent nerves during filling. Caffeine administered intravesically had no effect on cystometric parameters. CONCLUSIONS: Oral caffeine administration results in detrusor overactivity and increased bladder sensory signaling in the mouse.

Comparison of intraprostatic ethanol diffusion using a microporous hollow fiber catheter versus a standard needle.

PURPOSE: Transurethral intraprostatic ethanol chemoablation of the prostate has shown promising preliminary clinical results for benign prostatic hyperplasia with some variability in clinical outcome. This is likely due to the uneven prostate diffusion caused by varying resistance of the tissue type in which the tip of the needle is embedded. We examined whether the distribution of the injectable in the canine prostate could be improved using a microporous hollow fiber catheter (Twin Star Medical, Minneapolis, Minnesota). MATERIALS AND METHODS: The prostate was exposed in 9 mongrel dogs. A single injection of 98% ethanol was delivered in each lobe using a microporous hollow fiber catheter and a standard needle. Prostates were harvested and fixed in 10% formalin. After injection 2.5 mm step sections were obtained and scanned. The ethanol induced tissue lesions were traced on hematoxylin and eosin sections. Three-dimensional reconstructions were created and the volume of each prostate lesion was calculated using stereology. RESULTS: Ethanol induced tissue changes were seen bilaterally in 8 of 9 ethanol injected prostates. In all cases the lesion created by microporous hollow fiber catheter injection was larger than that in the contralateral lobe injected with the control needle. When data were pooled, the hollow fiber catheter injection produced significantly greater tissue changes than the control needle injection (p = 0.03). CONCLUSIONS: Improved distribution and absent backflow were seen when using the microporous hollow fiber catheter, supporting its potential as a new method to treat prostate disease.