Is the Brainstem Activation Different Between Healthy Young Male and Female Volunteers at Initiation of Voiding? A High Definition 7-Tesla Magnetic Resonance Imaging Study.

PURPOSE: Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. METHODS: Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as "initiation of voiding." BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. RESULTS: We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. CONCLUSION: Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

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.

Altered bladder-related brain network in multiple sclerosis women with voiding dysfunction.

OBJECTIVES: A number of neurourology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamic study (UDS)/functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥6 months and symptomatic voiding phase neurogenic lower urinary tract dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two UDS phases: "strong desire to void" and "(attempt at) voiding initiation." RESULTS: At "strong desire to void," the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During "(attempt at) voiding initiation," healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. CONCLUSION: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients.

Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study.

BACKGROUND: Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD. METHODS: We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p < 0.01). KEY RESULTS: Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze. CONCLUSIONS & INFERENCES: Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.

Prospective Evaluation of Intradetrusor Injections of OnabotulinumtoxinA in Adults With Spinal Dysraphism.

OBJECTIVE: To prospectively evaluate the effectiveness of OnabotulinumtoxinA (BTX-A) on neurogenic overactive bladder (nOAB) in adults with congenital spinal dysraphism (CSD). METHODS: We conducted a prospective, nonrandomized pilot study of 24 adults with CSD and neurogenic overactive bladder. Patients were evaluated with baseline video-urodynamics (UDS) and validated questionnaires, underwent injection 200U BTX-A, and then underwent repeat evaluation with questionnaires and UDS 1-3 months postinjection. A high-risk subgroup was separately analyzed based on adverse clinical characteristics (ie, decrease bladder compliance, vesicoureteral reflux, hydronephrosis, chronic kidney disease). RESULTS: BTX-A injection improved patient recorded outcome measures seen in both I-QOL Score total (67.9 vs 75.5, P = .007) and Neurogenic Bladder Symptom Score total (38.0 vs 29.0, P = .001). On UDS, BTX-A injection significantly improved end filling pressure (16.0 vs 8.8, P = .036) and also improved bladder compliance (mL/cm H2O) (89.38 vs 135.81, P = .445). High-risk patients were found to have similar improvements in most subjective questionnaire scoring, a significant decrease in end filling pressures, and improved bladder compliance on UDS. CONCLUSION: BTX-A can be used as an effective treatment in adults with CSD. We found that BTX-A significantly improved quality of life from patient reported outcome measurements as well as improving end filling pressures and bladder compliance. These improvements were seen even within our high-risk subgroup. Further studies are needed to evaluate long-term efficacy and appropriate follow-up of this at-risk population.

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.

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial.

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.

Dissecting the role of radical cystectomy and urinary diversion in post-operative complications: an analysis using the American College of Surgeons national surgical quality improvement program database

ABSTRACT 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<0.001) and without RC (34.0% vs 22.0%, p=0.032). Conclusions: RC+UD, as compared to UD alone, is associated with an increased risk of major complications, including bleeding needing transfusion and venous thromboembolism. Additionally, CUD had a higher risk of post-operative complication than IC.

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.

Dissecting the role of radical cystectomy and urinary diversion in post-operative complications: an analysis using the American College of Surgeons national surgical quality improvement program database.

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< 0.001) and without RC (34.0% vs 22.0%, p=0.032). CONCLUSIONS: RC+UD, as compared to UD alone, is associated with an increased risk of major complications, including bleeding needing transfusion and venous thromboembolism. Additionally, CUD had a higher risk of post-operative complication than IC.

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial.

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).

High spatial correlation in brain connectivity between micturition and resting states within bladder-related networks using 7 T MRI in multiple sclerosis women with voiding dysfunction.

BACKGROUND: Several studies have reported brain activations and functional connectivity (FC) during micturition using functional magnetic resonance imaging (fMRI) and concurrent urodynamics (UDS) testing. However, due to the invasive nature of UDS procedure, non-invasive resting-state fMRI is being explored as a potential alternative. The purpose of this study is to evaluate the feasibility of utilizing resting states as a non-invasive alternative for investigating the bladder-related networks in the brain. METHODS: We quantitatively compared FC in brain regions belonging to the bladder-related network during the following states: 'strong desire to void', 'voiding initiation (or attempt at voiding initiation)', and 'voiding (or continued attempt of voiding)' with FC during rest in nine multiple sclerosis women with voiding dysfunction using fMRI data acquired at 7 T and 3 T. RESULTS: The inter-subject correlation analysis showed that voiding (or continued attempt of voiding) is achieved through similar network connections in all subjects. The task-based bladder-related network closely resembles the resting-state intrinsic network only during voiding (or continued attempt of voiding) process but not at other states. CONCLUSION: Resting states fMRI can be potentially utilized to accurately reflect the voiding (or continued attempt of voiding) network. Concurrent UDS testing is still necessary for studying the effects of strong desire to void and initiation of voiding (or attempt at initiation of voiding).

Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia.

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.

Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction?

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.

Voiding Dysfunction in Old Male Rats Associated With Enlarged Prostate and Irregular Afferent-Triggered Reflex Responses.

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 receptors. METHODS: 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. CONCLUSION: 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.

Refractory bladder dysfunction: A multi-institutional experience with intravesical botulinum toxin-a injection in adult patients who underwent previous augmentation cystoplasty.

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.

Brain activation patterns of female multiple sclerosis patients with voiding dysfunction.

AIMS: We compared brain activation patterns between female multiple sclerosis (MS) patients with voiding dysfunction (VD) and those without. We aim to expand current knowledge of supraspinal correlates of voiding initiation within a cohort of female MS patients with and without VD. MATERIALS AND METHODS: Twenty-eight ambulatory female MS patients with stable disease and lower urinary tract dysfunction were recruited for this study. Subjects were divided into group 1, without VD (n = 14), and group 2, with VD (n = 14), defined as postvoid residual urine of ≥40% of maximum cystometric capacity or need for self-catheterization. We recorded brain activity via functional magnetic resonance imaging (fMRI) with simultaneous urodynamic testing. Average fMRI activation maps (the Student t test) were created for both groups, and areas of significant activation were identified (P < .05). A priori regions of interest (ROIs), identified by prior meta-analysis to be involved in voiding, were selected. RESULTS: Group-averaged blood-oxygen level-dependent (BOLD) activation maps demonstrated significant differences between groups 1 and 2 during initiation of voiding with group 2 showing significantly lower levels of activation in all ROIs except for the left cerebellum and right cingulate gyrus. Interestingly, group 2 displayed negative BOLD signals, while group 1 displayed positive signals in the right and left pontine micturition center, right periaqueductal gray, left thalamus, and left cingulate gyrus. The activation map of group 1 was similar to healthy controls. CONCLUSIONS: Our results support the hypothesis that distinct supraspinal activation patterns exist between female MS patients with VD and those without.