Central Control Circuit for Context-Dependent Micturition.

Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.

PIEZO2 in sensory neurons and urothelial cells coordinates urination.

Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination1-3, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow4. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.

A Pilot Study of the Effect of Transcutaneous Spinal Cord Stimulation on Micturition-Related Brain Activity and Lower Urinary Tract Symptoms After Stroke.

PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.

Impact of age and anterior fibromuscular stroma preservation on post-enucleation voided volume.

PURPOSE: This study is centered on the critical role of anterior fibromuscular stroma (AFS) preservation in prostate enucleation, an emerging strategy aimed at minimizing postoperative urinary incontinence-a common concern in benign prostatic hyperplasia (BPH) surgeries. By focusing on postoperative voiding volumes (VV), our research investigates the efficacy of AFS preservation. This approach, distinct in its methodology, is hypothesized to improve urinary function post-surgery, thereby offering a potentially significant advancement in BPH surgical treatments. MATERIALS AND METHODS: A retrospective analysis was conducted, comparing patients who underwent prostate enucleation in 2017 without intentional AFS preservation to those in 2019 with this technique. We examined variables including age, BMI, diabetes, hypertension, and preoperative VV to assess their effect on post-catheter removal VV. The study's methodology includes a thorough review of the primary statistical analysis methods employed. RESULTS: Our analysis indicates that while the 2017 and 2019 cohorts were similar in most preoperative parameters, the 2019 group that underwent AFS-preserved surgery showed a significant improvement in postoperative VVs. This was less pronounced in the patient group aged over 70, underscoring the importance of this demographic in our study. CONCLUSIONS: The study concludes that intentional preservation of AFS during prostate enucleation positively impacts early postoperative VVs, with limited improvement in older patients. These findings highlight the potential of AFS preservation not only in enhancing urinary outcomes post-surgery but also in shaping future BPH surgical procedures and research directions.

Antegrade ejaculation preservation in surgical treatment for benign prostatic hyperplasia: quest for balance between voiding and sexual function.

PURPOSE OF REVIEW: Surgical treatment of benign prostatic hyperplasia (BPH) carries a significant risk of ejaculation dysfunction. Preservation of antegrade ejaculation while providing effective, well tolerated, and durable treatment of BPH is a paramount component of physical and sexual well being for significant number of men. We reviewed available literature with an aim of providing status on antegrade ejaculation preserving BPH surgical therapies. RECENT FINDINGS: Minimally invasive surgical therapies for BPH have been developed over the last decade, with significant marketing emphasis on their potential for preservation of antegrade ejaculation. However, the question about durability of relief of bladder outlet obstruction remains. Parallel to this technological development, the understanding of anatomical structures involved in ejaculation have resulted in technical modifications of well established surgical treatments modalities like transurethral resection of prostate, endoscopic enucleation of prostate and simple prostatectomy, thereby providing safe and durable relief of bladder outlet obstruction secondary to BPH with a satisfactory preservation of antegrade ejaculation. SUMMARY: Preservation of antegrade ejaculation is an important goal for significant number of men needing BPH surgery. Novel minimally invasive surgical technologies have been developed for this purpose; but understanding of the anatomical structures essential for antegrade ejaculation have allowed technical modification of existing surgical techniques with excellent preservation of antegrade ejaculation.

Can we increase the value of data from bladder diaries? International Consultation on Incontinence-Research Society 2023.

BACKGROUND: Bladder diaries represent a fundamental component in the assessment of patients presenting with lower urinary tract symptoms. Nevertheless, their importance often remains underappreciated and undervalued within clinical practice. This paper aims to conduct a comprehensive review of the existing literature concerning the utility of bladder diaries, underscore the criticality of their precision, elucidate the factors contributing to noncompliance with bladder diary completion, and investigate potential strategies for enhancing patient compliance. MATERIALS AND METHODS: A review of the English-language scientific literature available in the domains of Medline, Embase, Emcare, Midirs, and Cinahl was conducted. This was supplemented by discussion at the International Consultation on Incontinence Research Society Proposal session to define knowledge and identify gaps in knowledge surrounding the utility of bladder diaries. The existing evidence and outcome of the relevant discussion held in the meeting are presented. RESULTS: Bladder diaries (BD) serve to characterize the nature and severity of storage lower urinary tract symptoms (LUTS) and provide an objective record of an individual's urination patterns. They aid in the refinement and customization of treatment strategies based on the clinical responses documented in the diary, optimizing treatment outcomes. Notably, both BD and urodynamic studies (UDS) play complementary yet distinct roles in LUTS evaluation. BD offers a more comprehensive and accessible approach to assessing specific storage LUTS, particularly due to their affordability and widespread availability, especially in resource-limited settings. Nevertheless, the absence of a standardized BD format across global healthcare systems presents a significant challenge. Despite being recognized as reliable, noninvasive, validated, and cost-effective tools for evaluating patients with LUTS, the implementation and completion of BD have proven to be complex. The introduction of automated bladder diaries heralds an era of precise, real-time data collection, potentially enhancing the patient-clinician relationship. Completion of bladder diaries depends on an array of individual, social, and healthcare-specific factors. Compliance with bladder diary completion could be enhanced with clear instructions, patient education, regular follow-ups and positive re-enforcement. This study has identified four critical areas for future research: Addressing healthcare disparities between affluent and developing nations, enhancing the current functionality and effectiveness of bladder diaries, exploring the feasibility of incorporating bladder diaries into the treatment and education process and improving the quality and functionality of existing bladder diaries. CONCLUSION: Bladder diaries play a pivotal role in the evaluation and management of patients with LUTS, providing a holistic perspective. When their complete potential is harnessed, they have the capacity to revolutionize the paradigm of LUTS management, ushering in a patient-centered era of care.

The association of lower urinary tract symptoms with schizophrenia and its treatments: A narrative review.

BACKGROUND: A higher incidence of lower urinary tract symptoms (LUTS) in people with schizophrenia compared to the general population is often suggested. However, it is not clear whether this is a genuine association, and whether it is a direct result of schizophrenia itself, or a side-effect of certain antipsychotics. METHODS: We undertook a narrative review evaluating how the published literature reports the relationship between LUTS and schizophrenia and its treatments. We searched Embase, Ovid Emcare, and Ovid MEDLINE(R) ALL to August 2022, limited to the English language. We selected the following search terms: schizophrenia, schizophrenic, LUTS, overactive bladder, urinary urgency, urinary incontinence, overactive bladder, enuresis, nocturnal enuresis, and voiding dysregulation. We identified seven domains for assessment in advance of commencing the review. These were the categorization, description, and treatment status of schizophrenia; evaluation of LUTS; categorization of LUTS confounders; recapturing of the disease states of both schizophrenia and LUTS after therapies; assessment of the association between LUTS and schizophrenia and/or antipsychotics. RESULTS: The association between LUTS and schizophrenia was poorly described. The evidence was low quality and focused predominantly on urinary incontinence as an antipsychotic side effect, neglecting other LUTS. The status of schizophrenia was often incompletely characterized, and no papers made use of a bladder diary or LUTS-specific questionnaires to assess symptoms. No papers collected information about LUTS in patients not on antipsychotics, nor did any thoroughly evaluate the influence of confounding variables. Despite the tendency of symptoms and severity of both conditions to fluctuate over time, no studies fully assessed the status of both schizophrenia and LUTS at baseline, therapy initiation, and follow-up. CONCLUSIONS: It is not possible to state whether there is an association between LUTS and schizophrenia or its treatments. This review highlights the need to improve research and clinical management of the urinary tract in schizophrenia, with meticulously designed longitudinal studies.

Assessment of Urinary Dysfunction After Midurethral Sling Placement: A Comparison of Two Voiding Trial Methods.

STUDY OBJECTIVE: Temporary urinary retention after midurethral sling (MUS) surgery requiring indwelling catheter or self-catheterization usage is common. Different methods for assessment of immediate postoperative urinary retention have been described. This study aimed to compare postoperative voiding trial (VT) success after active vs passive VT in women undergoing MUS surgery. DESIGN: Comparative retrospective cohort study. SETTING: Female pelvic medicine and reconstructive surgery practice at a university-affiliated tertiary medical center. PATIENTS: Patients with stress urinary incontinence who underwent surgical treatment during the study period were eligible for inclusion. Excluded were patients younger than the age of 18 years, combined cases with other surgical services, planned laparotomy, and a history of urinary retention and patients for whom their VT was performed on postoperative day 1. The cohort was divided into 2 groups: (1) patients who underwent an active retrofill of their bladder using a Foley catheter and (2) patients who were allowed to have a spontaneous void. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 285 patients met the inclusion criteria for the study. Of these subjects, 94 underwent an active VT and 191 underwent a passive VT. There were no statistically significant differences in immediate postoperative urinary retention (30.8% vs 29.3%; p = .79) or time from surgery end to VT (233.0 ± 167.6 minutes vs 203.1 ± 147.8 minutes; p = .13) between groups. Urinary retention, as defined by a failed VT, increased from 10% to 29.3% when MUS placement was accompanied by concomitant prolapse repair procedure. Multivariate logistic regression analysis revealed that undergoing a combined anterior and posterior colporrhaphy (odds ratio [OR], 5.13; p <.001) and undergoing an apical prolapse procedure (OR, 2.75; p = .004) were independently associated with immediate postoperative urinary retention whereas increased body mass index (OR, 0.89; p <.001) lowered likelihood of retention. CONCLUSION: The method used to assess immediate postoperative urinary retention did not affect VT success. Concomitant combined anterior and posterior colporrhaphy and apical suspension were correlated with greater likelihood of VT failure whereas increased body mass index decreased odds of retention.

Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.

Long-Term and Short-Interval Assessment of Self-Reported Urinary and Sexual Functions after Nerve-Sparing Radical Hysterectomy: A Prospective Cohort Study.

The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

Voiding dynamics of pelvic organ prolapse: Large scale comparative study.

PURPOSE: To determine the voiding dynamics of the patients with pelvic organ prolapse (POP). MATERIALS AND METHODS: A retrospective patient file review was performed of 877 female patients with lower urinary tract symptoms. After exclusion criteria 373 female patients were eligible for the study. Two patient groups w/wo prolapse were identified. The symptoms, patient characteristics, patterns of free urine flow, and detrusor voiding pressure curves were compared between two groups. A comparison of the urodynamic findings between the subgroups (mild/moderate, severe, and w/o prolapse) was made and shown on a scatter plot graphics of Pdet Qmax versus Qmax as well. RESULTS: A total of 373 patients with median age 54 (18-92), 189 (51%) had varying degrees and forms of POP while 184 (49%) did not have any prolapse (p < 0.003). Logistic regression analysis results showed that older age [p = 0.023, odds ratio (OR) = 1.01, confidence interval (CI): (1.00-1.03)], weaker pelvic floor muscle strength [p = 0.032, OR = 1.67, CI: (1.04-2.69)], more frequent symptom of hesitancy [p = 0.003 OR = 2.15 CI: (1.29-3.58)], prolonged-tailed shaped curve pattern of free urine flow [p = 0.027 OR = 1.97 CI: (1.08-3.58)], and higher Pdet Qmax (22 cmH2 O) values [p = 0.002, OR = 1.02, CI: (1.00-1.03)] were the independent different features of the patients with prolapse. Subgroup urodynamic analysis showed significantly lower free flowmetry Qmax and higher Pdet Qmax values in patients with severe prolapse. Prolonged/tailed-shaped curve pattern of free urine flow was significantly more frequent in patients with prolapse. CONCLUSIONS: Voiding dynamics of the patients with prolapse were significantly different from the patients' w/o prolapse. They had higher Pdet Qmax values, more frequent symptom of hesitancy, and prolonged shaped free flow curve pattern. Free flow Qmax values were lower in patients with severe prolapse.

Noninvasive brain stimulation in the treatment of functional urological and pelvic floor disorders: A scoping review.

INTRODUCTION: Functional pelvic floor disorders (PFD) such as bowel and bladder dysfunctions can be challenging to manage with our current therapeutic modalities. Recently, noninvasive brain stimulation has emerged as a novel strategy for noninvasive pelvic floor management. Here, we assessed the current state of research on this topic. METHODS: A scoping review was conducted with Pubmed, Web of Science, and Embase, in conjunction with clinicaltrials.gov, encompassing all manuscripts published without past time limit up until June 30, 2022. RESULTS: Of the 880 abstracts identified in a blind selection by two reviewers, 14 publications with an evidence level of 1 or 2 (Oxford scale) were eligible and included in this review. Review articles, case reports (<5 patients), letters, and protocol studies were excluded. PFDs were described as either pelvic pain or lower urinary tracts symptoms (LUTS) with repeated transcranial magnetic stimulation (rTMS) as the most common treatment modality. Despite heterogeneous therapeutic protocols, significant improvements were observed such as reduction in postvoid residual of urine, increased bladder capacity, improved voiding flow paraments, and decreased chronic pelvic, and bladder pain. No appreciable adverse effects were noted. However, low sample populations allowed only provisional conclusions. CONCLUSION: Noninvasive transcranial neurostimulation for LUTS and pelvic pain is emerging as an effective tool for clinicians to utilize in the future. Further investigation is needed to elucidate the full significance of the indicated outcomes.

ICS-SUFU standard: Theory, terms, and recommendations for pressure-flow studies performance, analysis, and reporting. Part 1: Background theory and practice.

AIMS: The working group (WG) initiated by the International Continence Society Standardization Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction has revised the (1997) ICS Standard for pressure flow studies. METHODS: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in January 2023 to facilitate public discussion and the comments received have been incorporated into this final release. RESULTS: The WG summarizes the theory and recommends the practice and the terms used for the diagnosis of voiding dysfunction for adult female and male patients without relevant neurological abnormalities, in part 1 of this standard. The WG has also recommended standard principles and parameters for objective and continuous grading of urethral resistance and detrusor voiding contraction on the basis of pressure flow studies in part 2. The recommendations for practice in this part have also the aim to increase the understanding of the physiology as well as the psychology of voiding. The potential effects of the laboratory situation of the test on the voiding as well as the role of the urodynamicist in this regard are discussed. The WG has recommended to use for diagnosis only the voidings that are considered representative by the patient. CONCLUSION: A pressure flow study is the gold standard to assess voiding function and to quantify dysfunction. This part of the standard explains the clinical background, gives recommendations for the execution of a pressure flow study and lists relevant terms, parameters, and units of measurements.

Reflex voiding in rat occurs at consistent bladder volume regardless of pressure or infusion rate.

AIMS: The central nervous system (CNS) regulates lower urinary tract reflexes using information from sensory afferents; however, the mechanisms of this process are not well known. Pressure and volume were measured at the onset of the guarding and micturition reflexes across a range of infusion rates to provide insight into what the CNS is gauging to activate reflexes. METHODS: Female Sprague Dawley rats were anesthetized with urethane for open outlet cystometry. A set of 10 infusion rates (ranging 0.92-65.5 mL/h) were pseudo-randomly distributed across 30 single-fill cystometrograms. Bladder pressure and external urethral sphincter electromyography were used for the determination of the onset of the micturition and guarding reflexes, respectively. The bladder volume at the onset of both reflexes was estimated from the total infusion rate during a single fill. RESULTS: In response to many single-fill cystometrograms, there was an increased volume the bladder could store without a significant increase in pressure. Volume was adjusted for this effect for the analysis of how pressure and volume varied with infusion rate at the onset of the micturition and guarding reflexes. In 25 rats, the micturition reflex was evoked at similar volumes across all infusion rates, whereas the pressure at micturition reflex onset increased with increasing infusion rates. In 11 rats, the guarding reflex was evoked at similar pressures across infusion rates, but the volume decreased with increasing infusion rates. CONCLUSIONS: These results suggest that the CNS is interpreting volume from the bladder to activate the micturition reflex and pressure from the bladder to activate the guarding reflex.

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.

Establishment of an overactive bladder model in mice.

BACKGROUND: Overactive bladder (OAB) is a syndrome characterized by symptoms of urinary urgency, often accompanied by frequent urination and nocturia or urge incontinence. METHODS: Twenty female ICR mice were randomly divided into pBOO (partial bladder outlet obstruction) and control groups. The mouse OAB model was constructed by ligating the bladder outlet. Eight weeks after the operation, the methods of voiding spot on paper (VSOP), isolated detrusor muscle, and HE staining were used for analysis and research. RESULTS: After the operation, two mice in the experimental and one in control died, and one in the control groups had an abnormal bladder size, so it was excluded from the statistical analysis. Eight weeks after the operation, there was an insignificant difference (P = 0.15) in the body weight of mice in the pBOO (26.54 ± 2.62 g) and the control group (24.84 ± 1.76 g). The number of urinations in 12 h was significantly higher (P < 0.001) in the pBOO (7.63 ± 1.19) than in the control group (4.13 ± 0.99). Also, the 12-h urine volume of pBOO (1491.23 ± 94.72 µL) was significantly greater (P = 0.006) than that of the control group (1344.86 ± 88.17 µL). The isolated bladder of the pBOO mice was significantly heavier than that in the control group (53.16 ± 1.79 mg vs. 24.54 ± 1.80 mg, P < 0.001), the horizontal and vertical length of the bladder in pBOO group were larger than those in the control group (P < 0.001). The detrusor thickness of pBOO group (357.50 ± 11.88 µm) was significantly thicker than that of control group (258.52 ± 17.22 µm, P < 0.001), and the isolated muscle strip was more sensitive to carbachol stimulation. According to HE staining, the bladder wall of the pBOO mice was significantly thickened. CONCLUSIONS: A pBOO-mediated mouse OAB model was successfully established by ligating the bladder outlet.

The effect of pelvic floor muscle training in women with functional bladder outlet obstruction.

INTRODUCTION AND HYPOTHESIS: Female voiding dysfunction is often due to bladder outlet obstruction (BOO). We investigated pelvic floor muscle training (PFMT) effectiveness in women with functional BOO. METHODS: This is a prospective study recruiting 63 women functionally obstructed, over 18yo, maximum flow rate (Qmax) less than 12 ml/sec, naïve of voiding treatment. Exclusion criteria were anatomical BOO, neurological condition, pelvic intervention, psychiatric or anticholinergic medication, diabetes mellitus and affected upper urinary tract. At baseline, women underwent uroflow, post void residual (PVR) measurement, cystoscopy, cystogram and urodynamic study (UDS) with pelvic electromyography (EMG). Blaivas-Groutz nomogram has been used to define obstruction. After diagnosis, patients underwent six-month PFMT. Re-evaluation was offered four weeks after end of treatment. Data were analyzed with SPSSv22.0. RESULTS: 63 women were recruited and 48 finally included. At baseline, 20 reported 3 urinary tract infections (UTIs) during last year, and 12 had one episode of urine retention. Median Qmax was 7.5 ml/sec and median PVR 110 ml. 40 women were obstructed. 16 (40%) had mild, 16 (40%) moderate and 8 (20%) severe obstruction. All subjects had an overactive pelvic floor on EMG. Obstructed women were re-evaluated. Median Qmax was 8.5 ml/sec, close to baseline (p = 0.16). Median PVR was 65 ml, reduced to baseline (p = 0.02). 33 (82.5%) remained obstructed, 22 (66.67%) with mild, 8 (24.24%) moderate and 3 (9.09%) severe obstruction. 7 (17.5%) were non-obstructed. 4 patients reported one UTI episode with no cases of retention. CONCLUSIONS: A 6 month PFMT reduced UTIs and PVR in women with functional BOO. Additionally, most patients had a de-escalation to milder obstruction.

Detailed Investigation of Bladder Diary Parameters During Sacral Neuromodulation in Patients With Overactive Symptoms.

AIMS: Sacral neuromodulation (SNM) is a well-accepted, minimally invasive modality for patients with overactive bladder (OAB). Successful response to SNM is defined as at least 50% improvement in key symptoms, evaluated in a bladder diary (BD). BDs provide much useful information on bladder behavior during daily life. The aim of this study is to investigate BD parameter changes during SNM therapy in patients with OAB. MATERIALS AND METHODS: The International Consultation on Incontinence Questionnaires (ICIQ)-BD was filled out by 34 patients with OAB, for three days at baseline and after three weeks of subthreshold sensory stimulation. The patients were considered responders for SNM when 50% improvement was seen in the BD. They underwent implantation of an internal pulse generator (IPG), and subsequently, an ICIQ-BD and a visual analog scale (VAS) evaluating bladder satisfaction during three days were filled out six weeks, six months, and one year after IPG implantation. RESULTS: IPGs were implanted in 29 patients (85%). The BD showed a significant decrease in 24-hour leakage at three weeks from 4.2 to 0.6 (-86%, p < 0.001), similar significant decreases at six weeks and six months, and at one year (-80%). Voided volume (VV) at corresponding bladder sensation codes was not different between baseline and at three weeks of tined-lead procedure (TLP) (p > 0.05), and at six weeks (p > 0.05), six months (p > 0.1), and one year of IPG (p > 0.08). After three weeks of TLP, urgency episodes decreased from 4.8 to 3.4 (-30%, p = 0.025), with 59% reduction at six-weeks IPG (p < 0.001) and 49% at six-months IPG (p = 0.013). At one year, a decrease from 4.7 to 2.3 (52% reduction, p = 0.017) was noted. VAS showed the strongest correlation with urgency (p < 0.001) and frequency (p = 0.006). No significant correlation was found with VV (p = 0.87). CONCLUSIONS: Our study describes how bladder sensation parameters change over time in patients on SNM. VV does not significantly increase, nor does frequency significantly decrease over the first year. Leaks and the percentage of urgency episodes significantly decrease, reaching a plateau level between six-weeks and six-months SNM.

Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder-urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.