The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Treatment and Follow-up.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Diagnosis and Evaluation.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Higher Neural Correlates in Patients with Multiple Sclerosis and Neurogenic Overactive Bladder Following Treatment with Intradetrusor Injection of OnabotulinumtoxinA.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury.

OBJECTIVES: To evaluate the role that intravesical P2X2/3 purinergic receptors (P2X2/3Rs) 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 kDy (cN); moderate) or 150 kDy (cN; severe); Sham rats had no injury. Evaluations on urethane-anesthetised rats were conducted at either 2 or 4 weeks after 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 or IPHFO in the Sham and moderate-SCI rats, although did increase the intercontractile interval (ICI). At 2 weeks after SCI, the Sham and moderate-SCI rats had significant LUT electromyographic activity during voiding, with a noticeable reduction in LUT electrical signals seen at 4 weeks after SCI. Intravesical inhibition of P2X2/3R increased the ICI in the Sham and moderate-SCI rats at both time-points, but had no effect on rats with severe SCI. The external urethral sphincter (EUS) showed strong and P2X2/3R-independent electrical signals in the Sham and moderate-SCI rats in the early SCI stage. At 4 weeks after SCI, the responsiveness of the EUS was significantly attenuated, independently of SCI intensity. CONCLUSIONS: This study shows 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.

Modern Theories of Pelvic Floor Support : A Topical Review of Modern Studies on Structural and Functional Pelvic Floor Support from Medical Imaging, Computational Modeling, and Electromyographic Perspectives.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Workflow for Visualization of Neuroimaging Data with an Augmented Reality Device.

Commercial availability of three-dimensional (3D) augmented reality (AR) devices has increased interest in using this novel technology for visualizing neuroimaging data. Here, a technical workflow and algorithm for importing 3D surface-based segmentations derived from magnetic resonance imaging data into a head-mounted AR device is presented and illustrated on selected examples: the pial cortical surface of the human brain, fMRI BOLD maps, reconstructed white matter tracts, and a brain network of functional connectivity.

Functional mapping of the pelvic floor and sphincter muscles from high-density surface EMG recordings.

INTRODUCTION AND HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessment of urethral support using MRI-derived computational modeling of the female pelvis.

INTRODUCTION AND HYPOTHESIS: This study aimed to assess the role of individual anatomical structures and their combinations to urethral support function. METHODS: 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. RESULT: 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. CONCLUSIONS: 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.

Pelvic Organ Prolapse in Female Patients Presenting to Transitional Urology Care Clinic.

PURPOSE: Patients with congenital genitourinary abnormalities are growing into adulthood and their expectations, especially in the areas of sexual function and fertility are creating unforeseen challenges for health care providers. We review the incidence and management of pelvic organ prolapse at our Transitional Urology Clinic. MATERIALS AND METHODS: This study is a retrospective chart review of the presentation and treatment of patients with clinically bothersome pelvic organ prolapse seen at our tertiary Transitional Urology Clinic during 2012 to 2015. RESULTS: Seven patients with a mean age of 22.8 years presented to our clinic with clinically bothersome prolapse. Four patients had myelomeningocele, 2 had sacral agenesis and 1 had bladder exstrophy. All were on self-catheterization. Three patients were sexually active and 1 had an intact uterus and desired fertility. Bothersome symptoms included vaginal bulge in 6 cases, difficult vaginal intercourse in 1 and difficult catheterization in 1. For the leading edge of Bp (anterior compartment) prolapse the median POP-Q (Pelvic Organ Prolapse Quantification System) stage was 3 (range 1 to 3), for Bp (posterior compartment) prolapse it was 1 (range 0 to 3) and for C (vaginal vault or cervical) prolapse it was 2 (range 1 to 3). Management included pessary in 1 case, hysterectomy with bilateral uterosacral ligament suspension in 4, sacrocolpopexy in 1 and observation in 1. Mean followup was 17.6 months (range 1 to 92). One of the 5 patients treated with surgical intervention had recurrence in the anterior compartment and vaginal vault. CONCLUSIONS: Females with congenital genitourinary anomalies present with pelvic organ prolapse at a much younger age and a more advanced stage. There is a paucity of literature on the epidemiology, presentation and management of pelvic organ prolapse in this patient population.

Inhibition of urothelial P2X3 receptors prevents desensitization of purinergic detrusor contractions in the rat bladder.

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.

Functional brain interactions during reflexive micturition are absent from spinal cord injured rats with neurogenic bladder.

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.

The Single-Incision Sling to Treat Female Stress Urinary Incontinence: A Dynamic Computational Study of Outcomes and Risk Factors.

Dynamic behaviors of the single-incision sling (SIS) to correct urethral hypermobility are investigated via dynamic biomechanical analysis using a computational model of the female pelvis, developed from a female subject's high-resolution magnetic resonance (MR) images. The urethral hypermobility is simulated by weakening the levator ani muscle in the pelvic model. Four positions along the posterior urethra (proximal, midproximal, middle, and mid-distal) were considered for sling implantation. The α-angle, urethral excursion angle, and sling-urethra interaction force generated during Valsalva maneuver were quantitatively characterized to evaluate the effect of the sling implantation position on treatment outcomes and potential complications. Results show concern for overcorrection with a sling implanted at the bladder neck, based on a relatively larger sling-urethra interaction force of 1.77 N at the proximal implantation position (compared with 0.25 N at mid-distal implantation position). A sling implanted at the mid-distal urethral location provided sufficient correction (urethral excursion angle of 23.8 deg after mid-distal sling implantation versus 24.4 deg in the intact case) with minimal risk of overtightening and represents the optimal choice for sling surgery. This study represents the first effort utilizing a comprehensive pelvic model to investigate the performance of an implanted sling to correct urethral hypermobility. The computational modeling approach presented in the study can also be used to advance presurgery planning, sling product design, and to enhance our understanding of various surgical risk factors which are difficult to obtain in clinical practice.

Functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating micturition.

PURPOSE: Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine centers, allowing the pontine micturition center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction. MATERIALS AND METHODS: We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects. RESULTS: Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the pontine micturition center with many short-range and long-range cortical clusters. CONCLUSIONS: Our study is one of the first reports of brain activation centers associated with micturition initiation in normal healthy females. Results show activation of a brain network consisting of regions for motor control, executive function and emotion processing. Further studies are planned to create and validate a model of brain activity during normal voiding in women.

The surgical learning curve of artificial urinary sphincter implantation: implications for prosthetic training and referral.

PURPOSE: We investigated the surgical learning curve of artificial urinary sphincter implantation using a large, consecutive, single surgeon series. MATERIALS AND METHODS: We retrospectively reviewed the results of the first 150 consecutive, virgin artificial urinary sphincter implantations performed by a single surgeon between 1992 and 2003 for post-prostatectomy male stress urinary incontinence. Complication and reoperation rates, and continence outcomes (daily pad use and number of patients with a functional artificial urinary sphincter at last followup) were analyzed as a function of consecutive implant cases. RESULTS: There was a significant decrease in the number of patients with complications (12 vs 3, relative risk 4.0, p = 0.012) and the number with reoperation (11 vs 3, relative risk 3.7, p = 0.026) when the first 25 patients who underwent artificial urinary sphincter implantation were compared to the second 25. No further decrease was noted beyond the first 25 cases. Despite significantly higher complication and reoperation rates in the first 25 cases, equivalent functional outcomes (same postoperative daily pad use and number of patients with a functional artificial urinary sphincter at last followup) were still achieved after artificial urinary sphincter revision. CONCLUSIONS: The surgical learning curve of placing a virgin artificial urinary sphincter was about 25 cases, as measured by complication and reoperation rates. This case number was high compared to typical exposure during residency and clinical practice. There is an urgent need to improve urological prosthetic training and emphasize the referral of artificial urinary sphincter cases to regional centers of excellence or to high volume, artificial urinary sphincter implanters to improve the surgical outcome.

Classification of multiple sclerosis women with voiding dysfunction using machine learning: Is functional connectivity or structural connectivity a better predictor?

Introduction: Machine learning (ML) is an established technique that uses sets of training data to develop algorithms and perform data classification without using human intervention/supervision. This study aims to determine how functional and anatomical brain connectivity (FC and SC) data can be used to classify voiding dysfunction (VD) in female MS patients using ML. Methods: Twenty-seven ambulatory MS individuals with lower urinary tract dysfunction were recruited and divided into two groups (Group 1: voiders [V, n = 14]; Group 2: VD [n = 13]). All patients underwent concurrent functional MRI/urodynamics testing. Results: Best-performing ML algorithms, with highest area under the curve (AUC), were partial least squares (PLS, AUC = 0.86) using FC alone and random forest (RF) when using SC alone (AUC = 0.93) and combined (AUC = 0.96) as inputs. Our results show 10 predictors with the highest AUC values were associated with FC, indicating that although white matter was affected, new connections may have formed to preserve voiding initiation. Conclusions: MS patients with and without VD exhibit distinct brain connectivity patterns when performing a voiding task. Our results demonstrate FC (grey matter) is of higher importance than SC (white matter) for this classification. Knowledge of these centres may help us further phenotype patients to appropriate centrally focused treatments in the future.

Complex artificial urinary sphincter revision and reimplantation cases--how do they fare compared to virgin cases?

PURPOSE: We compared artificial urinary sphincter complication rates, overall reoperative rates, and continence results in virgin cases, revision cases and secondary reimplant cases (with prior erosion or infection). MATERIALS AND METHODS: Only male patients with post-prostatectomy stress incontinence with AMS 800™ placement in the bulbar urethra by a single surgeon were included in the study. A total of 169 virgin cases (no prior artificial urinary sphincter surgery), 37 revision cases (eg cuff revision for urethral atrophy, revision of failed components) and 21 secondary reimplant cases (eg after prior explant from urethral erosion or infection) were compared. RESULTS: Secondary artificial urinary sphincter reimplant cases (eg after prior explant from urethral erosion or infection) had fourfold higher future erosion rates compared to virgin cases (p = 0.02, 14.3% vs 3.6%, RR 4.02). In addition, there was no difference in the rates of other complications (device infection, urethral atrophy, mechanical failure, leaks), overall reoperation rates and postoperative continence outcomes (measured by daily pad use) compared to virgin cases. Artificial urinary sphincter revision cases did not have higher complication rates (including subsequent urethral erosion), reoperation rates or worse postoperative continence outcomes compared to virgin cases. Although the difference was not statistically significant, a trend toward higher future device leak rates (10.8% vs 3.6%, RR 3.05, p = 0.063) and higher urethral atrophy rates (16.2% vs 8.9%, RR 1.83, p = 0.18) was noted in artificial urinary sphincter revision cases compared to virgin implant cases. CONCLUSIONS: Patients with a history of artificial urinary sphincter explant have a fourfold increased risk of future cuff erosion. Nevertheless, a good functional outcome with an acceptable complication rate may be achieved in most complex reoperative artificial urinary sphincter cases.

Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors.

OBJECTIVE: To evaluate the role of bladder sensory purinergic P2X3 and P2X2/3 receptors on modulating the activity of lumbosacral neurones and urinary bladder contractions in vivo in normal or spinal cord-injured (SCI) rats with neurogenic bladder overactivity. MATERIALS AND METHODS: SCI was induced in female rats by complete transection at T8-T9 and experiments were performed 4 weeks later, when bladder overactivity developed. Non-transected rats were used as controls (normal rats). Neural activity was recorded in the dorsal horn of the spinal cord and field potentials were acquired in response to intravesical pressure steps via a suprapubic catheter. Field potentials were recorded under control conditions, after stimulation of bladder mucosal purinergic receptors with intravesical ATP (1 mm), and after intravenous injection of the P2X3/P2X2/3 antagonist AF-353 (10 mg/kg and 20 mg/kg). Cystometry was performed in urethane-anaesthetised rats intravesically infused with saline. AF-353 (10 mg/kg) was systemically applied after baseline recordings; the rats also received a second dose of AF-353 (20 mg/kg). Changes in the frequency of voiding (VC) and non-voiding (NVC) contractions were evaluated. RESULTS: SCI rats had significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increased field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduced this parameter in both groups. AF-353 also reduced the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced. CONCLUSION: The P2X3/P2X2/3 receptors on bladder afferent nerves positively regulate sensory activity and NVCs in overactive bladders.

Preliminary Analysis of Brain Footprints in Multiple Sclerosis Females With Detrusor Sphincter Dyssynergia: A Concurrent Urodynamic and Functional Magnetic Resonance Imaging Study.

PURPOSE: This study evaluates the grey and white brain matter characteristics in women with multiple sclerosis (MS) and detrusor sphincter dyssynergia (DSD). Grey matter is assessed via the functional connectivity (FC) of brain regions activated during voiding, using functional magnetic resonance imaging (fMRI). Two white matter tracts involved in bladder function, the anterior thalamic radiation (ATR) and superior longitudinal fasciculus (SLF), were evaluated using diffusion tensor imaging. METHODS: Twenty-seven women with MS (2 groups: no-DSD [n=23] or DSD [n=4]), and 8 healthy controls (HCs) underwent concurrent urodynamic-fMRI evaluation with 4 cycles of bladder filling and emptying. A FC similarity measure (FC_sim) was calculated for each subject to express the similarity of individual FC at voiding initiation compared to all FC patterns. ATR and SLF tracts were traced and their fractional anisotropy (FA) and mean diffusivity (MD) were recorded. RESULTS: Mean FC_sim values were significantly different among the 3 groups indicating distinct FC patterns; however, no significant difference was found between DSD and no-DSD groups. DSD group showed trends of lower FA and higher MD- indicating loss of coherence-in all tracts compared to HCs, and in the left and right ATR when compared to MS women with neither DSD nor voiding dysfunction (VD), suggesting more damage in these tracts for MS women with DSD. CONCLUSION: Women with MS show distinctly different FC patterns compared to HCs. There are trends showing more damage in the ATR in women with MS and DSD compared to those with neither DSD nor VD.