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The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management.A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base.This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed.NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.

Objective Augmentation cystoplasty is a treatment option for neurogenic lower urinary tract dysfunction as well as severe, refractory, complicated idiopathic overactive bladder. In some patients, symptoms may persist or recur postoperatively, and there is little guidance on management in this setting. In this study, we reviewed the use of intravesical onabotulinum toxin type A (BTX-A) in patients who had undergone augmentation cystoplasty. Material and methods Retrospective chart review was performed at two institutions, identifying patients who underwent augmentation cystoplasty and were subsequently treated with intravesical BTX-A. Demographics, and preoperative and postoperative findings were collected. Results In total, 21 (16 female, 5 male) patients (mean age: 37.2 years) with previous augmentation cystoplasty were identified. In 17 patients with urodynamic data, mean maximum cystometric capacity was 312 mL, and decreased compliance and detrusor overactivity were noted in 53% and 48% patients, respectively. Combined intradetrusor/intra-augment injections were performed in 11 patients, and the remaining 10 patients received detrusor-only injections. A total of 18 patients (86%) reported subjective improvement with no significant difference associated with site of injection (p=0.59). A total of 17 patients (77%) underwent repeat injections; on average, patients underwent 3.3 injections with interval of 8.8 months between injections. Conclusion BTX-A injection was shown to subjectively improve storage symptoms and continence after augmentation cystoplasty in the majority of patients. In this cohort, patients had good subjective response regardless of site of injection, and most patients benefited from repeat injections. Prospective studies are needed to better evaluate the efficacy and ideal sites of BTX-A injection in the setting of refractory voiding dysfunction following augmentation cystoplasty.

PURPOSE: Voiding dysfunction (VD) leading to urinary retention is a common neurogenic lower urinary tract symptom in patients with multiple sclerosis (MS). Currently, the only effective management for patients with MS with VD is catheterization. Transcranial Rotating Permanent Magnet Stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions and the strength of their functional connections. In this pilot trial (ClinicalTrials.gov Identifier: NCT03574610), we investigated the safety and therapeutic effects of TRPMS in modulating brain regions of interest (ROIs) engaged with voiding initiation to improve VD in MS women. MATERIALS AND METHODS: Ten MS women with VD (having % post-void residual/bladder capacity [%PVR/BC] ≥40% or being in the lower 10th percentile of the Liverpool nomogram) underwent concurrent functional magnetic resonance imaging/urodynamic study (fMRI/UDS) with 3 cycles of bladder filling/emptying, at baseline and post-treatment. Predetermined ROIs and their activations at voiding initiation were identified on patients’ baseline fMRI/UDS scans, corresponding to microstimulator placement. Patients received 10 consecutive 40-minute treatment sessions. Brain activation group analysis, noninstrumented uroflow, and validated questionnaires were compared at baseline and post-treatment. RESULTS: No treatment-related adverse effects were reported. Post-treatment, patients showed significantly increased activation in regions known to be involved at voiding initiation in healthy subjects. %PVR/BC significantly decreased. Significant improvement of bladder emptying symptoms were reported by patients via validated questionnaires. CONCLUSIONS: Both neuroimaging and clinical data suggested TRPMS effectively and safely modulated brain regions that are involved in the voiding phase of the micturition cycle, leading to clinical improvements in bladder emptying in patients with MS.

The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management.A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base.This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician.NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.

Objective: To characterize the contribution of the extirpative and reconstructive portions of radical cystectomy (RC) to complications rates, and assess differences between urinary diversion (UD) types. Materials and Methods: We conducted a retrospective cohort study comparing patients undergoing UD alone or RC+UD for bladder cancer from 2006 to 2017 using ACS National Surgical Quality Improvement Program database. The primary outcome was major complications, while secondary outcomes included minor complications and prolonged length of stay. Propensity score matching (PSM) was utilized to assess the association between surgical procedure (UD alone or RC+UD) and outcomes, stratified by diversion type. Lastly, we examined differences in complication rates between ileal conduit (IC) vs. continent UD (CUD). Results: When comparing RC + IC and IC alone, PSM yielded 424 pairs. IC alone had a lower risk of any complication (HR 0.63, 95% CI 0.52-0.75), venous thromboembolism (HR 0.45, 95% CI 0.22-0.91) and bleeding needing transfusion (HR 0.41, 95% CI 0.32-0.52). This trend was also noted when comparing RC + CUD to CUD alone. CUD had higher risk of complications than IC, both with (56.6% vs 52.3%, p = 0.031) and without RC (47.8% vs 35.1%, p=0.062), and a higher risk of infectious complications, both with (30.5% vs 22.7%, p

Purpose To quantify the relative importance of brain regions responsible for reduced functional connectivity (FC) in their Voiding Initiation Network in female multiple sclerosis (MS) patients with neurogenic lower urinary tract dysfunction (NLUTD) and voiding dysfunction (VD). A data-driven machine-learning approach is utilized for quantification. Methods Twenty-seven ambulatory female patients with MS and NLUTD (group 1: voiders, n=15 and group 2: VD, n=12) participated in a functional magnetic resonance imaging (fMRI) voiding study. Brain activity was recorded by fMRI with simultaneous urodynamic testing. The Voiding Initiation Network was identified from averaged fMRI activation maps. Four machine-learning algorithms were employed to optimize the area under curve (AUC) of the receiver-operating characteristic curve. The optimal model was used to identify the relative importance of relevant brain regions. Results The Voiding Initiation Network exhibited stronger FC for voiders in frontal regions and stronger disassociation in cerebellar regions. Highest AUC values were obtained with 'random forests' (0.86) and 'partial least squares' algorithms (0.89). While brain regions with highest relative importance (>75%) included superior, middle, inferior frontal and cingulate regions, relative importance was larger than 60% for 186 of the 227 brain regions of the Voiding Initiation Network, indicating a global effect. Conclusion Voiders and VD patients showed distinctly different FC in their Voiding Initiation Network. Machine-learning is able to identify brain centers contributing to these observed differences. Knowledge of these centers and their connectivity may allow phenotyping patients to centrally focused treatments such as cortical modulation.

Background Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals. Methods Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement. Discussion Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future. Trial registration This trial is registered at ClinicalTrials.Gov (NCT03574610, 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329)

Objectives Two white matter tracts (WMTs) are proposed to be involved in bladder function: anterior thalamic radiation and superior longitudinal fasciculus. Multiple sclerosis (MS) patients with voiding dysfunction (VD) may have distinct changes in these 2 WMTs. This study aims to compare the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging of MS females with and without VD versus healthy controls (HCs). Methods Prospective observational cohorts of 28 female MS patients and 11 HCs were recruited. Multiple sclerosis patients were divided into 2 groups: voiders (patients without VD, n = 14) and VD (patients with VD, n = 14). Diffusion tensor imaging of each subject was obtained, from which FA and MD maps were generated. The mean FA and MD of each WMT on both sides were analyzed using one-way analysis of variance and pairwise comparison with adjusted P values. Results Overall MS patients had significantly lower mean FA (loss of coherence) and significantly higher mean MD (increased free diffusion) than HCs in both WMTs, indicating more damage. Furthermore, VD showed a trend of loss of integrity in both WMTs when compared with voiders with lower FA and higher MD. Conclusions There is damage reflected by lower FA and higher MD values in the proposed WMTs involved in bladder function in MS women. Voiding dysfunction in this patient population can be attributed to these damages considering women with VD demonstrated a trend of deterioration in these WMTs compared with women without VD. Future studies with larger sample sizes should be done to further confirm this correlation.

Purpose: This study was conducted to evaluate the hypothesis that an enlarged prostate in old rats may lead to complications associated with voiding dysfunction involving ionotropic P2X2/3-type purinergic receptorsMethods: Intact animals were divided into male young (MYR; 8–10 weeks old) and male old (MOR; 20 months old) rats. The animals underwent simultaneous detrusor electromyography (EMG) and suprapubic cystometry (CMG) under urethane anesthesia. Immunofluorescence techniques were used to evaluate prostatic autonomic innervation and P2X3R expression in bladder urothelial cells. The functional role of P2X3R was characterized by intramuscular application of AF-353, a selective P2X2/3R antagonist.Results: The prostate index significantly increased in MOR, suggestive of an enlarged prostate affecting micturition patterns. Significant EMG and CMG differences were found between MYR and MOR. Higher immunoreactivity for P2X2/3R in the urothelial layer and for prostatic neurofilaments was seen in MOR. Systemic inhibition of P2X2/3R had minimal effects on MYR responsiveness, but improved voiding function in MOR with a marked decrease of intravesical pressure and bladder contractile responses.Conclusions: The data support the hypothesis that an enlarged prostate in MOR may contribute to voiding dysfunction involving activation of P2X2/3R, which enhances a prostate-bladder reflex. This reflex may increase bladder afferent transmission and activation of increased prostate innervation, leading to voiding dysfunction.

INTRODUCTION AND OBJECTIVE:OnabotulinumtoxinA (BTX-A) injection is a well-established management strategy in the treatment of patients with neurogenic overactive bladder (NOAB). Few studies, howeve...

AIM: To investigate if Multiple Sclerosis (MS) lesion characteristics affect functional brain connectivity (FC) during bladder voiding. METHODS: Twenty-seven ambulatory female patients with MS completed our functional magnetic resonance imaging (fMRI)/urodynamic testing (UDS) platform. Individual fMRI activation maps were generated at initiation of voiding. FC patterns of these regions were calculated and compared. Similarity of the FC pattern from one patient relative to all others was expressed by a parameter FC_sim. A statistical analysis was performed to reveal the relationship of the existence of an enhancing brain lesion, the size of the largest lesion and the ability to void spontaneously to this FC similarity measure. RESULTS: FC_sim values were significantly lower for patients with an enhancing MS lesion (11.7 ± 3.1 vs 5.3 ± 2.1 P < 0.001). Lesion size smaller than 20 mm inversely correlated significantly with FC_sim (R = −0.43, P = 0.05). Patients with the ability to void spontaneously had a higher FC_sim value (12.0 ± 2.8 vs 9.3 ± 4.4 s, P = 0.08). Patients that exhibited a decrease of compliance also showed a significantly lower FC_sim value (11.3 ± 3.5 vs 4.7 ± 0.7, P < 1e-5). CONCLUSION: FC connectivity analysis derived from an fMRI task-based study including repetitive voiding cycles is able to quantify the heterogeneity of connectivity patterns in the brain of MS patients. FC similarity decreased with maximum lesion size or the presence of enhancing lesions affecting the ability to void spontaneously.

Purpose To characterize the electromyographic activity of abdominal striated muscles during micturition in urethane-anesthetized female mice, and to quantitatively evaluate the contribution of abdominal responses to efficient voiding. Methods Cystometric and multichannel electromyographic recordings were integrated to enable a comprehensive evaluation during micturition in urethane-anesthetized female mice. Four major abdominal muscle domains were evaluated: the external oblique, internal oblique, and superior and inferior rectus abdominis. To further characterize the functionality of the abdominal muscles, pancuronium bromide (25 μg/mL or 50 μg/mL, abdominal surface) was applied as a blocking agent of neuromuscular junctions. Results We observed a robust activation of the abdominal muscles during voiding, with a consistent onset/offset concomitant with the bladder pressure threshold. Pancuronium was effective, in a dose-dependent fashion, for partial and complete blockage of abdominal activity. Electromyographic discharges during voiding were significantly inhibited by applying pancuronium. Decreased cystometric parameters were recorded, including the peak pressure, pressure threshold, intercontractile interval, and voiding duration, suggesting that the voiding efficiency was significantly compromised by abdominal muscle relaxation. Conclusions The relevance of the abdominal striated musculature for micturition has remained a topic of debate in human physiology. Although the study was performed on anesthetized mice, these results support the existence of synergistic abdominal electromyographic activity facilitating voiding in anesthetized mice. Further, our study presents a rodent model that can be used for future investigations into micturition-related abdominal activity.

Purpose To simultaneously monitor electrical discharges in various bladder regions and the external urethral sphincter (EUS) during voiding contractions, and to assess the functional role of myogenic modulation of the lower urinary tract (LUT) by ionotropic purinergic receptors containing the P2X3 subunit. Methods Female Sprague-Dawley rats were anesthetized with urethane, and implanted with a suprapubic catheter for open cystometry. Flexible microelectrodes were placed ventrally in the bladder dome, upper bladder, lower bladder, and bladder base, along with the middle section of the exposed EUS. Intravesical P2X3-containing receptors were blocked with AF-323, a specific P2X3-P2X2/3 receptor antagonist. A digital electrophysiology amplifier was used to record electrical and cystometric signals throughout the LUT. Results Electrical activity in the LUT started before effective voiding contractions. Bladder pressure and electrical waveforms showed consistent out-of-phase activity when compared with the recordings made at the EUS. This pattern was also observed during voiding contractions in the presence of AF-353, supporting the hypothesis that during bladder distension, activation of P2X3-containing receptors is required for voiding contractions. Furthermore, the inhibition of P2X3-containing receptors significantly decreased the amplitude of electrical signals in the urinary bladder, but not the base or EUS. Conclusions Our results provide novel information about the regulation of the micturition process by P2X3-containing receptors located in the inner layers of the bladder.

PURPOSE OF REVIEW: Voiding dysfunction (VD) is morbid, costly, and leads to urinary tract infections, stones, sepsis, and permanent renal failure. Evaluation and diagnosis of VD in non-obstructed patients can be challenging. Potential diagnostic and therapeutic options beyond the bladder, such as brain centers involved in voiding have been proposed as promising targets. This review focuses on current and future applications of functional neuroimaging in human in voiding and in patients with VD. RECENT FINDINGS: The current understanding of brain centers, and their roles in initiating, maintaining and/or modulating voiding, is rudimentary in humans and in patients with VD. With the advent and advancement in functional neuroimaging we are gaining more insight into specific brain regions involved in the voiding phase of micturition. In healthy individuals, right dorsomedial pontine tegmentum, periaqueductal grey, hypothalamus, and the inferior, medial and superior frontal gyrus have been identified as regions of interest in voiding. SUMMARY: Functional neuroimaging could suggest new diagnostic methods and provides crucial steps towards therapeutic options for the morbid and intractable VD condition, in patients with neurogenic (e.g. MS or Strokes) or non-neurogenic VD (e.g. underactive bladder or Fowler’s syndrome).

Artificial urinary sphincters (AUS) are common. Life expectancy at average implantation (71.5 years) is 14 years. During this period patients must still possess manual dexterity and cognitive capabilities needed to operate the AUS, otherwise it is practically unfunctional. Still, available data regarding AUS durability deal with medical and mechanical factors. Issues as age-related deteriorating manual dexterity and cognitive capabilities precluding patients from operating an apparently intact AUS have not been addressed. We set to focus on these aspects. We review the natural history of manual dexterity, physical, and cognitive deterioration of aging men and propose counseling and screening algorithms for evaluating these aspects.

Objectives Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS. Methods Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values. Results The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%. Conclusions The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS.

INTRODUCTION AND OBJECTIVES:Many Multiple Sclerosis (MS) patients have Voiding Dysfunction (VD). Since MS lesions mainly affect the white matter, we decided to evaluate the integrity of the two proposed white matter tracts (WMT) involved in proper lower urinary tract (LUT) function: Anterior thalamic radiation (ATR) and the Superior longitudinal fasiculus (FSL). We seek to compare the fractional anisotropy (FA) and mean diffusivity (MD) from the Diffusion Tensor Imaging (DTI) brain scans of female MS patients who are voiders versus patients with VD versus Healthy Control (HC). We hypothesized that MS females with VD have lower FA and higher MD than voiders, and MS patients overall have lower FA and higher MD than HCs in these specific WMTs.METHODS:Twenty-eight female MS patients and eleven HCs were recruited for this study. MS patients were divided into two groups: Group 1; patients without VD (n=15) who void spontaneously and their postvoid residual of urine < 40% Maximum Cystometric Capacity (MCC), and ...

Knowledge of the innervation of pelvic floor and sphincter muscles is of great importance to understanding the pathophysiology of female pelvic floor dysfunctions. This report presents our high-density intravaginal and intrarectal electromyography (EMG) probes and a comprehensive innervation zone (IZ) imaging technique based on high-density EMG readings to characterize the IZ distribution. Both intravaginal and intrarectal probes are covered with a high-density surface electromyography electrode grid (8 × 8). Surface EMG signals were acquired in ten healthy women performing maximum voluntary contractions of their pelvic floor. EMG decomposition was performed to separate motor-unit action potentials (MUAPs) and then localize their IZs. High-density surface EMG signals were successfully acquired over the vaginal and rectal surfaces. The propagation patterns of muscle activity were clearly visualized for multiple muscle groups of the pelvic floor and anal sphincter. During each contraction, up to 218 and 456 repetitions of motor units were detected by the vaginal and rectal probes, respectively. MUAPs were separated with their IZs identified at various orientations and depths. The proposed probes are capable of providing a comprehensive mapping of IZs of the pelvic floor and sphincter muscles. They can be employed as diagnostic and preventative tools in clinical practices.

Introduction: Baseline urodynamic characterization in patients with neurogenic lower urinary tract dysfunction (NLUTD) allows detection of unsafe storage and voiding pressures and optimization of these parameters through medical or surgical intervention. Surveillance urodynamics (sUDS) studies are performed in the ambulatory setting after baseline characterization, with the goal of monitoring bladder function. How often this study should be performed and the circumstances that should prompt repeated studies are unknown. The primary objective of this review is to evaluate the evidence supporting sUDS in the setting of NLUTD as assessed by whether the study leads to 1) change in patient management; 2) determination of new findings not suggested by imaging or symptoms; and 3) demonstration of superior outcomes compared to observation. The secondary objective is to review sUDS practice patterns among urologists in their assessment of NLUTD. Methods: PubMed, EMBASE, and Cochrane Library databases were reviewed for English-language literature published between January 1975 and March 2018. Results: Twenty-eight independent articles (1368 patients, 9486 patient-years of followup) were included. Given heterogeneous data, 49% of 263 subjects were asymptomatic, yet demonstrated sUDS abnormality prompting treatment. Eight cross-sectional studies (four spinal cord injury [SCI], two NLUTD, two spina bifida) surveyed urologists regarding current sUDS patterns; 53% of 498 respondents perform sUDS between one and three years. Conclusions: Evidence supporting optimal surveillance for NLUTD is lacking. Level 2b‒4 evidence suggests that sUDS is likely to modify patient treatment and often demonstrates findings that modify treatment in the absence of symptoms or imaging changes.

OBJECTIVES: To evaluate the role that intravesical P2X2/3 purinergic receptors (P2X2/3R) play in early and advanced neurogenic lower urinary tract (LUT) dysfunction after contusion spinal cord injury (SCI) in female rats. MATERIALS AND METHODS: Female Sprague-Dawley rats received a thoracic Th8/Th9 spinal cord contusion with either force of 100 kDynes (kDy; moderate) or 150 kDynes (severe); Sham animals had no injury. Evaluations on urethane-anesthetized rats were at either two or four weeks post-SCI. LUT electrical signals and changes in bladder pressure were simultaneously recorded using cystometry and a set of custom-made flexible microelectrodes before and after intravesical application of the P2X2/3R antagonist AF-353 (10 μM) to determine the contribution of P2X2/3R-mediated LUT modulation. RESULTS: Severe SCI significantly increased bladder contraction frequency, and reduced both bladder pressure amplitude and intraluminal-pressure high-frequency oscillations (IPHFO). Intravesical P2X2/3R inhibition did not modify bladder pressure nor IPHFO in Sham and moderate SCI animals, although did increase intercontractile interval. At two weeks after SCI, Sham and moderate-SCI animals presented significant LUT electromyographic activity during voiding, with a noticeable reduction in LUT electrical signals observed at four weeks post-SCI. Intravesical inhibition of P2X2/3R increased the intercontractile interval in Sham and moderate SCI rats at either time point, but had no effect on animals with severe SCI. The external urethral sphincter (EUS) showed strong, and P2X2/3R-independent electrical signals in either Sham or moderate-SCI rats in the early SCI stage. At four weeks post-SCI the responsiveness of the EUS was significantly attenuated, independently of SCI intensity. CONCLUSIONS: This study demonstrates that electrophysiological properties of the LUT are progressively impaired depending on SCI intensity and that intravesical P2X2/3R inhibition can attenuate electrical activity in the neurogenic LUT at early, but not at semi-chronic SCI. This translational study should be useful for planning clinical evaluations.

Introduction: We aimed to evaluate sexual function, sexual knowledge, and fertility status in adult patients with congenital genitourinary abnormalities (CGUA). Methods: Adult patients with CGUA who were referred to a single transitional urology clinic between 2014 and 2017 were prospectively recruited to participate in the study. Questionnaires about general demographics, bowel and bladder continence, fertility, and sexuality were gathered. Validated questionnaires, including the Sexual Health Inventory for Men (SHIM) and Brief Index of Sexual Functioning for Women (BISF-W), were also collected. Results: A total of 167 adults with CGUA were referred to our clinic within the defined time frame. Sixty patients (25 males, 35 females) with a mean age of 25.4 years (range 18–75) met inclusion criteria and responded to questionnaires pertaining to sexuality and fertility. Forty-five (75%) responded to the fertility questionnaire; 26 (58%) had never heard of assisted reproductive technologies, and only one had received prior fertility counselling. Fifty-eight participants (97%) responded to the sexuality questionnaire; 21 (36%) reported a history of sexual activity, with 12 (21%) being currently sexually active. Twenty (34%) wanted to learn more about sexuality and/or fertility. The SHIM response rate was 44%, and only three females (9%) completed the BISF-W in its entirety. Conclusions: Adults with CGUA desire more sexuality and fertility education, yet they are uncomfortable completing current questionnaires. Our sexuality and fertility questionnaires are too challenging for this patient population to complete despite assistance. Thus, modifications are urgently needed. Additionally, medical providers should discuss sexual and reproductive health with these patients earlier and in more detail.

OnabotulinumtoxinA is a well described treatment of neurogenic overactive bladder. While motor effects on the detrusor muscle have been extensively studied, the sensory effects have not. The aim of this study was to evaluate the impact of intradetrusor onabotulinumtoxinA injection on brain activity in female patients with multiple sclerosis and neurogenic overactive bladder.We prospectively studied 12 women with stable multiple sclerosis and neurogenic overactive bladder using concurrent functional magnetic resonance imaging and urodynamic studies prior to and 6 to 10 weeks following onabotulinumtoxinA injection. Individual functional magnetic resonance imaging activation maps at the time of strong urgency were averaged before and after onabotulinumtoxinA injection where areas of significant activation were identified.After onabotulinumtoxinA injection functional magnetic resonance imaging activation increased in the right cingulate body (p = 0.0012), the left posterior cingulate (p = 0.02), the left anterior cingulate (p = 0.0015), the right prefrontal cortex (p = 0.0015), the insula (p = 0.0138) and the pons micturition center (p = 0.05). Sparse areas showed decreased activity, including the left cerebellum (p = 0.001), the left fusiform gyrus (p = 0.065) and the bilateral lentiform nucleus (p = 0.026).Intradetrusor injection of onabotulinumtoxinA appeared to increase the activity of most brain regions known to be involved in the sensation and process of urinary urgency in female patients with multiple sclerosis and neurogenic overactive bladder. To our knowledge this is the first study of its kind to evaluate the possible effects of onabotulinumtoxinA at the human brain level where sensory awareness is located. This activation pattern may be used to further phenotype patients to optimize therapy or determine the sensory effects of onabotulinumtoxinA beyond the bladder.

Background: Natural disasters take a heavy toll not only on their victims, but also on physicians who suffer vicarious trauma and burnout. New trainees in Houston, from entering PGY1 residents to entering fellows, underwent even more upheaval and stress during Hurricane Harvey. Many responded to calls for volunteer help. Objective: To investigate the impact of Hurricane Harvey on new trainees at our institution, and correlate volunteerism with measures of burnout and resilience. Methodology: Thirty three new trainees out of 90 (43% of population) from all specialties in our institution voluntarily responded to an online survey on the impact of Hurricane Harvey on their lives, whether or not they volunteered and in what form, and answered questions drawing from the abbreviated Maslach burnout survey and Resiliency Quiz. Statistical analyses were conducted using GraphPad Prism and Excel data analysis. Results: The top areas impacted were emotional health (32%), eating habits (29%), family (25%) and finances (25%). The main voluntary activities were covering for colleagues who could not make it to hospital (50%), donating money and supplies (36%), and cleaning and rebuilding (36%). Volunteering was associated with feelings of appreciation (76%), happiness (62%), thankfulness (57%), purposefulness (43%) and pride (33%). Fewer volunteers scored lowly in personal achievement as compared to non-volunteers (10 vs. 38%, p = 0.05). Significance: Hurricane Harvey affected health, finances and family of new trainees, more than half of whom volunteered to help. Volunteers had a greater sense of personal achievement as compared to non-volunteers. This may be due to having more volunteers among less burnt-out trainees or because volunteering reduced burnout and stress responses/trauma. These results suggest that volunteer opportunities should be made available in programs targeting resident burnout.

Weakened pelvic floor support is believed to be the main cause of various pelvic floor disorders. Modern theories of pelvic floor support stress on the structural and functional integrity of multiple structures and their interplay to maintain normal pelvic floor functions. Connective tissues provide passive pelvic floor support while pelvic floor muscles provide active support through voluntary contraction. Advanced modern medical technologies allow us to comprehensively and thoroughly evaluate the interaction of supporting structures and assess both active and passive support functions. The pathophysiology of various pelvic floor disorders associated with pelvic floor weakness is now under scrutiny from the combination of (1) morphological, (2) dynamic (through computational modeling), and (3) neurophysiological perspectives. This topical review aims to update newly emerged studies assessing pelvic floor support function among these three categories. A literature search was performed with emphasis on (1) medical imaging studies that assess pelvic floor muscle architecture, (2) subject-specific computational modeling studies that address new topics such as modeling muscle contractions, and (3) pelvic floor neurophysiology studies that report novel devices or findings such as high-density surface electromyography techniques. We found that recent computational modeling studies are featured with more realistic soft tissue constitutive models (e.g., active muscle contraction) as well as an increasing interest in simulating surgical interventions (e.g., artificial sphincter). Diffusion tensor imaging provides a useful non-invasive tool to characterize pelvic floor muscles at the microstructural level, which can be potentially used to improve the accuracy of the simulation of muscle contraction. Studies using high-density surface electromyography anal and vaginal probes on large patient cohorts have been recently reported. Influences of vaginal delivery on the distribution of innervation zones of pelvic floor muscles are clarified, providing useful guidance for a better protection of women during delivery. We are now in a period of transition to advanced diagnostic and predictive pelvic floor medicine. Our findings highlight the application of diffusion tensor imaging, computational models with consideration of active pelvic floor muscle contraction, high-density surface electromyography, and their potential integration, as tools to push the boundary of our knowledge in pelvic floor support and better shape current clinical practice.

This study aimed to assess the role of individual anatomical structures and their combinations to urethral support function.A realistic pelvic model was developed from an asymptomatic female patient's magnetic resonance (MR) images for dynamic biomechanical analysis using the finite element method. Validation was performed by comparing simulation results with dynamic MR imaging observations. Weaknesses of anatomical support structures were simulated by reducing their material stiffness. Urethral mobility was quantified by examining urethral axis excursion from rest to the final state (intra-abdominal pressure = 100 cmH2O). Seven individual support structures and five of their combinations were studied.Among seven urethral support structures, we found that weakening the vaginal walls, puborectalis muscle, and pubococcygeus muscle generated the top three largest urethral excursion angles. A linear relationship was found between urethral axis excursions and intra-abdominal pressure. Weakening all three levator ani components together caused a larger weakening effect than the sum of each individually weakened component, indicating a nonlinearly additive pattern. The pelvic floor responded to different weakening conditions distinctly: weakening the vaginal wall developed urethral mobility through the collapsed vaginal canal, while weakening the levator ani showed a more uniform pelvic floor deformation.The computational modeling and dynamic biomechanical analysis provides a powerful tool to better understand the dynamics of the female pelvis under pressure events. The vaginal walls, puborectalis, and pubococcygeus are the most important individual structures in providing urethral support. The levator ani muscle group provides urethral support in a well-coordinated way with a nonlinearly additive pattern.

Objective To compare the results of various single-component artificial urinary sphincter (AUS) revision techniques for continued/recurrent stress urinary incontinence (SUI). Although AUS placement for male SUI has a high rate of success, revisions may be performed for mechanical failure of an isolated component or continued/recurrent SUI. Materials and Methods From 1993 to 2012, 90 AUS revisions including urethral cuff downsizing (19), pressure-regulating balloon replacement (18), cuff repositioning (11), or tandem cuff placement (42) were performed at 2 institutions. End points included reoperation, incontinence failure, and urethral erosion. The Kruskal-Wallis test was used to compare continuous variables, and the log-rank test was used to compare Kaplan-Meier curves. Results Mean age was 70.2 years, and median follow-up was 33.6 months. Median time to revision was 28.9 months. Tandem cuff placement was associated with a lower rate of incontinence failure (P = .02), whereas cuff repositioning was associated with a higher rate of incontinence failure (P = .02). An increased rate of mechanical failure was observed with cuff downsizing (P = .01). Among options for revision (1) cuff downsizing is associated with a higher rate of mechanical failure, and (2) cuff repositioning with the same size is associated with a higher rate of incontinence failure, whereas (3) tandem cuff placement is associated with a lower rate of recurrent SUI compared to other types of AUS revision. Conclusion Cuff repositioning is associated with an increased rate of persistent incontinence after AUS revision whereas tandem cuff placement is associated with a lower rate of recurrent or persistent incontinence.

Objectives To evaluate whether P2X3 receptors (P2X3R) are expressed in the bladder urothelium and to determine their possible function in modulating purinergic detrusor contractions in the rat urinary bladder. Materials and Methods The expression of urothelial receptors was determined using conventional immunohistochemistry in bladders from normal Sprague–Dawley rats. The urothelial layer was removed by incubation with protamine, and disruption of the urothelium was confirmed using haematoxylin and eosin staining on bladder sections. Open cystometry was used to determine the effects of both urothelial removal as well as intravesical application of a specific P2X3R antagonist on bladder properties from intact and protamine-treated rats. Isometric contractile responses to potassium chloride (KCl) depolarization, electrical field stimulation (EFS) or chemical P2X activation were determined in normal and urothelium-denuded bladder strips, with and without application of the P2X3R antagonist. Results Immunohistochemical staining showed high expression of P2X3R in the medial and basal layers of the urothelium. Removal of the urothelial layer disturbed normal bladder performance in vivo and eliminated the effects of the P2X3R antagonist on increasing the contractile interval and reducing the amplitude of voiding contractions. Removal of the urothelium did not affect bladder strip contractile responses to KCl depolarization or EFS. Pharmacological inhibition of P2X3R prevented desensitization to P2X-mediated detrusor muscle contractions during EFS only in the strips with an intact urothelium. A concentration-dependent, specific inhibition of P2X3R also prevented desensitization of purinergic contractile responses in intact bladder strips. Conclusions In the rat bladder, medial and basal urothelial cells express P2X3R, and specific inhibition of the receptor leads to a more hyporeflexive bladder condition. This pathway may involve P2X3R driving a paracrine amplification of ATP released from umbrella cells to increase afferent transmission in the sub-urothelial sensory plexus and desensitization of P2X1-mediated purinergic detrusor contractions.

To determine if the timing of radiation therapy on artificial urinary sphincter (AUS) impacts complication rates, revision rates, and number of pads per day after placement.A retrospective review was conducted of men with prostate cancer who underwent AUS placement and radiation therapy between 1987 and 2016.Of 306 men, 292 (95.4%) received radiation before AUS placement (group 1) and 14 (4.6%) received radiation after AUS placement (group 2). Median follow-up was 30 months after AUS placement. Group 1 had 32 of 292 (11.0%) patients suffer from erosion, compared with 0 of 14 (0.0%) patients in group 2 (P = .191). None of the patients in group 2 had infection or mechanical failure. The number of patients who received revision in group 1 was 91 of 292 (31.2%) and in group 2 was 2 of 14 (14.3%) (P = .180). The number of pads used per day in group 1 before and after AUS placement was 5.24 ± 3.12 and 1.13 ± 1.31, respectively (P .001). In group 2, the number of pads used per day before and after AUS placement was 6.09 ± 1.97 and 1.53 ± 0.99, respectively (P .001). There was no significant difference in the average number of postoperative pads used per day between group 1 and group 2 (P = .907).The timing of radiation therapy does not appear to significantly affect complication rates or urinary continence, as measured in pads used after AUS placement. This multi-institutional retrospective analysis showed similar erosion and revision rates when radiation occurred after AUS placement and demonstrates preliminary safety and feasibility of the administration of radiation after AUS placement.

Aims The external anal sphincter (EAS) is essential for maintaining fecal continence. Neurological disorders or traumatic injuries to muscle and nervous systems could lead to EAS denervation. Currently, there are no techniques available to document global innervation changes in the EAS in vivo. The aim of this study was to develop a novel approach to non-invasively estimate the number of functioning motor units (MUs) in the EAS and validate with immunofluorescent techniques in rats. Methods Intra-rectal surface electromyography (EMG) signals of the EAS, induced by a series of intra-vaginally delivered pudendal nerve stimulations with different intensities, were recorded. Variation in EMG responses at different intensities was used to estimate the value of a single motor unit potential (SMUP) in order to perform the proposed EAS motor unit number estimation (MUNE) approach. The EAS MUNE was tested in 12 female Sprague-Dawley rats, and validated by comparing against the EAS myofiber counting results achieved by performing immunostaining of acetylcholine receptors in 7 of the 12 rats. Results The mean MU number was 35 ± 9, with an averaged SMUP size of 52.49 ± 20.39 μV. The mean number of successfully identified myofibers was 652.7 ± 130.6 myofiber/EAS. Significance of linear regression between the immunofluorescent results and the MUNE was confirmed (P

Aims The micturition reflex is initiated by urinary bladder distension triggering afferent pathways and activation of specific brain centers for controlling urine storage and release. We evaluated brain activation patterns using blood oxygenation level dependent functional magnetic resonance imaging (fMRI) during reflexive micturition in normal and spinal cord injury (SCI) rats. Methods Sprague-Dawley female rats, either intact or with complete spinal cord transection, were anesthetized with urethane for simultaneous isovolumetric cystometry (CMG) and fMRI evaluations. A 9.4-Tesla MRI system with a 4-elements receiver array and a quadrature volume transmit coil was used to maximize the sensitivity detection. Gradient echo-planar imaging (EPI) was used to evaluate brain activation during CMG compared to the empty bladder condition. Group analysis was conducted with a cluster threshold of Z > 2.5 and significance threshold of P = 0.05. Results The amplitude of bladder contractions was 10-fold higher in control rats and inter-contractile intervals were significantly shorter in SCI rats, indicative of neurogenic overactivity. Group analysis in intact rats showed both known and novel activation patterns in hippocampus, dentate gyrus, ectorhinal cortex, thalamic nucleus, septal nucleus, primary and secondary motor cortex, primary somatosensory cortex, and the periaqueductal gray matter. SCI rats did not exceed the Z-threshold during CMG. Conclusions We standardized a suitable urodynamic protocol to study supraspinal activation during reflexive micturition using simultaneous CMG/fMRI with high spatial resolution. Small contractions in SCI rats may be caused by increased excitability of afferent pathways without brain activation. Our results represent the first fMRI study in SCI rats. Neurourol. Urodynam. 34:469–474, 2015. © 2014 Wiley Periodicals, Inc.

Objective To issue a consensus document on the prevention, management, and research of infection associated with penile prostheses, as neither professional associations nor governmental entities have issued guidelines that are specific to this infection. Methods Sixteen North American experts on infection of penile prostheses were identified and assembled to select and discuss certain issues related to infection of penile prostheses. After performing an extensive search of clinically important issues in published reports, the 16 experts met twice in person to finalize the selection, discuss the issues that were deemed most important, and issue pertinent recommendations. Results Although many subjects relevant to infection of penile prostheses were initially identified, the experts selected 10 issues as currently being the most important issues and for which there exists some support in the published data. The examined issues involved prevention, management, or research of infections associated with penile prostheses. Conclusion In the absence of pertinent guidelines, the consensus document issued by experts in the field of prosthetic urology is anticipated to improve the quality of patient care, streamline the prevention and management of infected penile prostheses, and stimulate collaborative research. Although this consensus document could serve as best practice recommendations, the lack of adherence to these recommendations would not indicate improper care.

Augmentation cystoplasty (AC) is a well-established technique for improving bladder compliance and capacity, preserving renal function, and minimizing incontinence due to severe detrusor overactivity. The popularity of AC has declined over the past decade due to the improved efficacy of other conservative therapies such as botulinum toxin. However, AC plays an important role in the management of refractory patients. Many patients requiring AC will also benefit from the creation of a continent catheterizable channel and bladder outlet surgery. Various augmentation and continent channel techniques are described, along with associated complications. In the appropriate patient, AC is an excellent treatment option that can improve bladder function and improve patients’ quality of life.

Stress urinary incontinence is a significant problem in young female athletes, but the pathophysiology remains unclear because of the limited knowledge of the pelvic floor support function and limited capability of currently available assessment tools. The aim of our study is to develop an advanced computer modeling tool to better understand the dynamics of the internal pelvic floor during highly transient athletic activities.Apelvic model was developed based on high-resolution MRI scans of a healthy nulliparous young female. A jump-landing process was simulated using realistic boundary conditions captured from jumping experiments. Hypothesized alterations of the function of pelvic floor muscles were simulated by weakening or strengthening the levator ani muscle stiffness at different levels. Intra-abdominal pressures and corresponding deformations of pelvic floor structures were monitored at different levels of weakness or enhancement.Results show that pelvic floor deformations generated during a jump-landing process differed greatly from those seen in a Valsalva maneuver which is commonly used for diagnosis in clinic. The urethral mobility was only slightly influenced by the alterations of the levator ani muscle stiffness. Implications for risk factors and treatment strategies were also discussed.Results suggest that clinical diagnosis should make allowances for observed differences in pelvic floor deformations between a Valsalva maneuver and a jump-landing process to ensure accuracy. Urethral hypermobility may be a less contributing factor than the intrinsic sphincteric closure system to the incontinence of young female athletes.

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction.We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia.Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively.We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention.