Optogenetic stimulation of neurons in the anterior cingulate cortex induces changes in intravesical bladder pressure and the micturition reflex.

Lower urinary tract (LUT) function is controlled by the central nervous system, including higher-order cognitive brain regions. The anterior cingulate cortex (ACC) is one of these regions, but the role of its activity in LUT function remains poorly understood. In the present study, we conducted optogenetic experiments to manipulate neural activity in mouse ACC while monitoring bladder pressure to elucidate how the activity of ACC regulates LUT function. Selective optogenetic stimulation of excitatory neurons in ACC induced a sharp increase in bladder pressure, whereas activation of inhibitory neurons in ACC prolonged the interval between bladder contractions. Pharmacological manipulation of ACC also altered bladder contractions, consistent with those observed in optogenetic experiments. Optogenetic mapping of the cortical area responsible for eliciting the increase in bladder pressure revealed that stimulation to ACC showed more potent effects than the neighboring motor cortical areas. These results suggest that ACC plays a crucial role in initiating the bladder pressure change and the micturition reflex. Thus, the balance between excitation and inhibition in ACC may regulate the reflex bidirectionally.

Real-time prediction of bladder urine leakage using fuzzy inference system and dual Kalman filtering in cats.

The use of electrical stimulation devices to manage bladder incontinence relies on the application of continuous inhibitory stimulation. However, continuous stimulation can result in tissue fatigue and increased delivered charge. Here, we employ a real-time algorithm to provide a short-time prediction of urine leakage using the high-resolution power spectrum of the bladder pressure during the presence of non-voiding contractions (NVC) in normal and overactive bladder (OAB) cats. The proposed method is threshold-free and does not require pre-training. The analysis revealed that there is a significant difference between voiding contraction (VC) and NVC pressures as well as band powers (0.5-5 Hz) during both normal and OAB conditions. Also, most of the first leakage points occurred after the maximum VC pressure, while all of them were observed subsequent to the maximum VC spectral power. Kalman-Fuzzy method predicted urine leakage on average 2.2 s and 1.6 s before its occurrence and an average of 2.0 s and 1.1 s after the contraction started with success rates of 94.2% and 100% in normal and OAB cats, respectively. This work presents a promising approach for developing a neuroprosthesis device, with on-demand stimulation to control bladder incontinence.

Chronic chemogenetic inhibition of TRPV1 bladder afferent promotes micturition recovery post SCI.

Spinal cord injury often results in chronic loss of micturition control, which is featured by bladder hyperreflexia and detrusor sphincter dyssynergia. Previous studies showed that treatment of capsaicin reduces non-voiding bladder contractions in multiple animal injury models and human patients. However, its underlying neural mechanisms remain largely unknown. Here, by injecting a RetroAAV into the bladder wall, we specifically targeted TRPV1+, a capsaicin receptor, bladder afferent neurons. Morphometric analysis revealed borderline increase of the soma size and significant spinal axon sprouting of TRPV1+ bladder afferent neurons post a complete T8 spinal cord crush. We further demonstrated that chronic chemogenetic inhibition of these DRG neurons improved micturition recovery after SCI by increasing voiding efficiency and alleviating bladder hyperreflexia, along with reduced morphological changes caused by injury. Our study provided novel insights into the structural and functional changes of TRPV1+ bladder afferent post SCI and further supports the clinical use of capsaicin as an effective treatment to improve bladder functions in patients with SCI.

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

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

Tactile stimulation of the perigenital region during manual bladder expression improved the urine stream in cats affected by upper motor neuron injury.

OBJECTIVE: The aim of the study was to evaluate whether the tactile stimulation of the perigenital region together with manual bladder expression (MBE) facilitated the urine stream in cats with acute or chronic upper motor neuron injury (UMNI). ANIMALS: 34 cats with UMNI having urinary retention. METHODS: All the cats had a complete neurologic examination, which determined the localization of the UMNI between T3 and L3. They were classified as chronic UMNI if the injury had occurred more than 3 days previously. The cats were divided equally into 2 groups: the M group (n = 17) managed with only MBE, and the MT group (17) managed with MBE and tactile stimulation. RESULTS: In both groups, all the cats affected by chronic UMNI resumed urination. The time required to obtain a urine stream in the chronic UMNI was 9.3 seconds in the M group and 3.1 seconds in the MT group (P < .05). In the cats affected by acute UMNI, a urine stream was achieved in 54% of the M group and 100% of the MT group (P < .05). The time to obtain a urine stream in the acute UMNI cats was 7.8 seconds in the M group and 3.75 seconds in the MT group (P < .05). CLINICAL RELEVANCE: Adding tactile stimulation of the perigenital region to the MBE improved the urine stream in cats affected by UMNI.

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

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

[Drug therapy targeting angiotensin II type 1 receptors in brain against frequent urination].

The production of angiotensin II (Ang II) in the brain plays important roles as neurotransmitter and neuropeptide. Central Ang II is involved in regulating various physiological processes, such as blood pressure and water homeostasis, via Ang II type 1 (AT1) receptors. We have demonstrated that Ang II induces frequent urination via AT1 receptors in the brain even at doses that does not seem to affect the blood pressure in animal experiment. Intracerebroventricular administration of Ang II was also found to reduce the bladder capacity without affecting the maximum voiding pressure, post voiding residual urine volume or voiding efficiency. Additionally, the activation of AT1 receptor downstream signal pathway (phospholipase C/protein kinase C/NADPH oxidase/superoxide anion) and suppression of GABAergic nervous system in the brain are involved in the mechanism underlying the central Ang II-inducted frequent urination. AT1 receptor blockers (ARBs) have been widely used to treat hypertension. We demonstrated that peripherally administered ARBs telmisartan, which can penetrate blood-brain barrier, exerted an inhibitory effect on central Ang II-inducted frequent urination. We present the possible drug therapy targeting AT1 receptors in the brain against frequent urination on the results obtained from our recent research work.

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

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

Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats.

Recent pre-clinical and clinical spinal cord epidural stimulation (scES) experiments specifically targeting the thoracolumbar and lumbosacral circuitries mediating lower urinary tract (LUT) function have shown improvements in storage, detrusor pressure, and emptying. With the existence of a lumbar spinal coordinating center in rats that is involved with external urethral sphincter (EUS) functionality during micturition, the mid-lumbar spinal cord (specifically L3) was targeted in the current study with scES to determine if the EUS and thus the void pattern could be modulated, using both intact and chronic complete spinal cord injured female rats under urethane anesthesia. L3 scES at select frequencies and intensities of stimulation produced a reduction in void volumes and EUS burst duration in intact rats. After chronic transection, three different subgroups of LUT dysfunction were identified and the response to L3 scES promoted different cystometry outcomes, including changes in EUS bursting. The current findings suggest that scES at the L3 level can generate functional neuromodulation of both the urinary bladder and the EUS in intact and SCI rats to enhance voiding in a variety of clinical scenarios.

Personalized Pre-clinic Nursing Telemedicine Visit: An Efficient and Efficacious Approach for Bowel and Bladder Dysfunction in Children.

OBJECTIVES: To evaluate the effectiveness and efficacy of a Registered Nurse (RN) led educational pre-clinic telephone call on compliance and outcomes in children with bowel and bladder dysfunction (BBD). METHODS: A retrospective chart review of a prospectively applied protocol in a single academic institution was performed for children aged 4-17 presenting with BBD. All children underwent a pre-clinic RN telemedicine visit where they were educated on pathophysiology of BBD, provided personalized urotherapy and bowel recommendations and instructed to complete pre-clinic questionnaires and voiding diaries. Patients were evaluated by a provider 4weeks following RN call. Data collected included compliance with forms, bowel management and need for imaging/testing, medications, and biofeedback. Patients were considered to improve with urotherapy alone if they were discharged from urology without the need for medications and/or biofeedback. RESULTS: In total, 277 patients completed an RN call and 224 patients attended a provider visit between December 2020 and June 2022. Mean age was 9.4years (3:1 Female to Male ratio). During the RN call, 154 (56%) patients had bowel management initiated. Of the 224 patients seen by a provider, 69% (n = 154) had symptom improvement or resolution with urotherapy alone. Thirty-eight patients (17%) enrolled in biofeedback with 7 (3%) completing all 8 sessions. Thirty-two patients (14%) required medication for daytime bladder symptoms. CONCLUSION: Our novel RN-led pre-clinic telemedicine visit demonstrates excellent compliance and patient outcomes for children with BBD and can reduce the use of unnecessary imaging, medications, and time-consuming treatments such as biofeedback.

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

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

A Scoping Review of Epidural Spinal Cord Stimulation for Improving Motor and Voiding Function Following Spinal Cord Injury.

Objectives: To identify and synthesize the existing evidence on the effectiveness and safety of epidural spinal cord stimulation (SCS) for improving motor and voiding function and reducing spasticity following spinal cord injury (SCI). Methods: This scoping review was performed according to the framework of Arksey and O'Malley. Comprehensive serial searches in multiple databases (MEDLINE, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, LILACS, PubMed, Web of Science, and Scopus) were performed to identify relevant publications that focused on epidural SCS for improving motor function, including spasticity, and voiding deficits in individuals with SCI. Results: Data from 13 case series including 88 individuals with complete or incomplete SCI (American Spinal Injury Association Impairment Scale [AIS] grade A to D) were included. In 12 studies of individuals with SCI, the majority (83 out of 88) demonstrated a variable degree of improvement in volitional motor function with epidural SCS. Two studies, incorporating 27 participants, demonstrated a significant reduction in spasticity with SCS. Two small studies consisting of five and two participants, respectively, demonstrated improved supraspinal control of volitional micturition with SCS. Conclusion: Epidural SCS can enhance central pattern generator activity and lower motor neuron excitability in individuals with SCI. The observed effects of epidural SCS following SCI suggest that the preservation of supraspinal transmission is sufficient for the recovery of volitional motor and voiding function, even in patients with complete SCI. Further research is warranted to evaluate and optimize the parameters for epidural SCS and their impact on individuals with differing degrees of severity of SCI.

Influence of transurethral catheters on urine pressure-flow relationships in males: A computational fluid-dynamics study.

BACKGROUND AND OBJECTIVE: In the field of urology, the pressure-flow study (PFS) is an essential urodynamics practise which requires the patient's transurethral catheterization during the voiding phase of micturition to evaluate the functionality of the lower urinary tract (LUT) and reveal the pathophysiology of its dysfunctionality. However, the literature evidences confusion regarding the interference of the catheterization on the urethral pressure-flow behaviour. METHODS: The present research study represents the first Computational Fluid-Dynamics (CFD) approach to this urodynamics issue, analysing the influence of a catheter in the male LUT through case studies which included the inter-individual and intra-individual dependence. A set of four three dimensional (3D) models of the male LUT, different in urethral diameters, and a set of three 3D models of the transurethral catheter, diverse in calibre, were developed leading to 16 CFD non-catheterized either catheterized configurations, to describe the typical micturition scenario considering both urethra and catheter characteristics. RESULTS: The developed CFD simulations showed that the urine flow field during micturition was influenced by the urethral cross-sectional area and each catheter determined a specific decrease in flow rate if compared to the relative free uroflow. CONCLUSIONS: In-silico methods allow to analyse relevant urodynamics aspects, which could not be investigated in vivo, and may support the clinical PFS to reduce uncertainty on urodynamic diagnosis.

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

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

A prospective cohort study of assisted bladder emptying following primary cloacal repair: The Children's National experience.

INTRODUCTION/BACKGROUND: Although the combination of bladder dysfunction and upper tract anomalies puts patient with cloaca at risk for renal disease, the rarity of this condition makes it difficult to study empirically. As a high-volume center, we uniquely capture bladder function outcomes following our growing number of cloacal repairs. OBJECTIVE: 1) Describe the rates of incomplete bladder emptying following primary cloacal repair (at 2-3 months after repair and last follow up), and 2) identify clinical factors associated with assisted bladder emptying. STUDY DESIGN: We performed a prospective cohort study of patients undergoing primary cloaca repair by our Children's National Colorectal Center team between 2020 and 2021. The primary outcome was assisted bladder emptying at 2-3 months postoperatively and last visit. Covariables included preoperative characteristics (cloacagram measurements), ARM complexity (moderate = common channel [CC] <3-cm, severe = CC ≥ 3-cm), vesicoureteral reflux (VUR) status, sacral ratio (good ≥0.7, intermediate 0.7-0.4, poor ≤0.4), spinal cord status, means of preoperative bladder emptying, and operative details (age at repair, repair type, & concomitant laparotomy). RESULTS: Eighteen participants were eligible. A majority had moderate cloaca (78%), VUR (67%), spinal cord abnormalities (89%), and good sacral ratios (56%). Preoperatively, 10 patients were diapered for urine and 8 had assisted bladder emptying. Surgical repairs were performed at a median age of 8 months (range 4-46). Nine (50%) patients underwent urogenital separation (UGS), eight (44%) total urogenital mobilization, and 1 (6%) perineal sparing posterior sagittal anorectoplasty with introitoplasty. Exploratory laparotomy was performed in 7 (39%) patients. At 2-3 months, 7 patients were voiding and 11 required assisted bladder emptying. Median length of long-term follow up was 12 months (range 5-25), and 8 patients were voiding and 10 required assisted bladder emptying. Postoperative need for assisted bladder emptying was significantly associated with assisted bladder emptying preoperatively, a shorter urethra and increasing common channel length, UGS and exploratory laparotomy. Spinal cord imaging findings were not associated. DISCUSSION: Bladder emptying following cloaca repair is likely a result of congenital function and surgical effects. Indeed, increasingly cloaca complexity requiring UGS and laparotomy was associated with both pre- and post-operative assisted bladder emptying. The lack of association with spinal cord imaging may reflect a divergence between anatomy and function. CONCLUSION: Approximately half of patients required assisted bladder emptying in this study. Associated factors included urethral and common channel length, the need for assisted bladder emptying preoperatively, the type of surgical approach and additional laparotomy. Being diapered with seemingly normal voiding prior to surgery did not guarantee normal bladder function postoperatively.

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

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

Functional MRI in neuro-urology: A narrative review.

Neuro-imaging has given urologists a new tool to investigate the neural control of the lower urinary tract. Using functional magnetic resonance imaging (fMRI), it is now possible to understand which areas of the brain contribute to the proper function of the storage and voiding of the lower urinary tract. This field of research has evolved from simple anatomical descriptions to elucidating the complex micturition network. A keyword search of the Medline database was conducted by two reviewers for relevant studies from January 1, 2010, to August 2022. Of 2047 peer-reviewed articles, 49 are included in this review. In the last decade, a detailed understanding of the brain-bladder network has been described, elucidating a dedicated network, as well as activated areas in the brainstem, cerebellum, and cortex that share reproducible connectivity patterns. Research has shown that various urological diseases can lead to specific changes in this network and that therapies used by urologists to treat lower urinary tract symptoms (LUTS) are also able to modify neuronal activity. This represents a set of potential new therapeutic targets for the management of the lower urinary tract symptoms (LUTS). fMRI technology has made it possible to identify subgroups of responders to various treatments (biofeedback, anticholinergic, neuromodulation) and predict favourable outcomes. Lastly, this breakthrough understanding of neural control over bladder function has led to treatments that directly target brain regions of interest to improve LUTS. One such example is the use of non-invasive transcranial neuromodulation to improve voiding symptoms in individuals with multiple sclerosis.

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

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

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

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

Establishment of an overactive bladder model in mice.

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