Traumatic brain injury and bladder function: From acute to chronic phase. A literature review

Traumatic brain injury (TBI) can induce a coma and directly affect the pathways that help control lower urinary tract (LUT) function. This paper reviews the clinical and urodynamic data from the literature on LUT function after TBI in the acute, rehabilitation and chronic phases. The number of papers available on LUT function after TBI is very limited, but the studies have been well conducted, and the sample size is acceptable. The interpretation of reported data is complex due to heterogeneity in the items studied and the level of detail. During the early phase, indwelling catheters are needed for critical care, but spontaneous voiding is possible in most patients as soon as the catheter can be removed. The ability to void is primarily independent of the Glasgow Coma Scale value. During rehabilitation, spontaneous voiding is observed in the majority, but re-learning of voluntary control may be needed. In the follow-up, complete recovery of continence and voiding is possible, but overactive bladder and other LUT symptoms (LUTS) have been described. The data show that afferent and sensory functions related to the LUT remain active in many TBI patients, making long-term use of indwelling catheters unnecessary. There are no studies that follow the evolution in the same patient over a long period. Urodynamic studies show that LUT function varies after TBI and that variables such as age, previous dysuria, diabetes and local anatomic pathologies can also influence the outcome. Personalized management after an evaluation is therefore needed in TBI patients

A pilot study to measure dynamic elasticity of the bladder during urodynamics

AIMS: Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics. METHODS: Patients reporting urgency most or all of the time based on ICIq-OAB survey scores were prospectively enrolled in an extended repeat fill-and-empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call dynamic elasticity. Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening. RESULTS: Five patients completed the extended urodynamics study. Intravesical pressure (p(ves)) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P=0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with p(ves) in Fill 4 returning to the baseline measured during Fill 1 (P=0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per %capacity (average p(ves) between fills/%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal). CONCLUSIONS: Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub-typing and novel treatments of overactive bladder

Onset of action of the beta 3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder

Purpose Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1–2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a b3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies. Methods This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV). Results A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated. Conclusions The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB

Developing new ways to assess neural control of pelvic organ function in spinal conditions: ICI-RS 2023

Objectives: Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms. Methods: This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction. Results: Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure? Conclusions: Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back

Neuromodulation and the role of electrodiagnostic techniques

Electrodiagnostic techniques have been utilized in surgery since the early 1960s. These techniques have been primarily used in neurosurgery; however, with the introduction of neuromodulation for voiding dysfunction, these techniques have now found their way into the field of female pelvic medicine. This article will review techniques applicable to evaluate pelvic floor function as it relates to neuromodulation. It will also review the literature describing how these techniques are used to help determine appropriate candidates as well as improve surgical outcomes. A PubMed search was conducted using the terms neuromodulation, Interstim, electrodiagnosis, electrodiagnostic techniques, electromyography with limits to the pelvic floor, and voiding dysfunction. Eight articles and three abstracts were found that directly related to the use of electrodiagnostic techniques as they apply to neuromodulation. Electrodiagnostic techniques may play a role in helping predict appropriate candidates for neuromodulation as well as improve surgical outcomes

Very long-term follow-up of Indiana Pouches proves durability

Introduction: An Indiana Pouch (IP) is a heterotopic, continent, urinary diversion from an ileocolonic segment. Numerous studies have investigated its long-term outcomes, albeit none extending beyond a 5-year follow-up period. IPs can be used as urinary diversion for benign indications and as such are constructed in typically young patients. As a consequence of their extended lifespan, there is a need for very long-term (>5 years) IP outcome data and comprehensive complication analysis. Materials and Methods: In this retrospective cohort study, the data of all patients attending our academic functional urology tertiary referral center for surveillance between 2015 and 2022 after an earlier IP procedure without uro-oncological indication were analyzed. The primary objective was to identify the prevalence of complications associated with IP, including stomal stenosis, ureter-pouch stenosis, pouch calculi, stomal leakage, pouch perforation, and parastomal herniation, and to determine the time span between creation of the IP and occurrence of complications. Results: A cohort of 33 patients (23 female) was analyzed. Median age at IP creation was 38 (range 5–62) years. Median follow-up was 258 (range 24–452) months. During follow-up, 22 (67%) patients underwent at least one surgical revision. In total, 45 revision procedures were performed. The estimated mean revision-free survival was 198 (95%-CI 144–242) months. Conclusion: Two-thirds of our IP patients required surgical revision during very long-term follow-up. However, the mean revision-free survival was 198 months. This establishes the IP as a durable and resilient option for urinary diversion, yet underlines the need for lifelong follow-up as some of these complications and indication were subclinical. These results contribute significantly to patient counseling when discussing different options for urinary diversion, especially at a younger age

A phase II dose-ranging study of mirabegron in patients with overactive bladder

Introduction and hypothesis Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder. Methods Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n=928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume. Results Mirabegron 25, 50, 100, and 200 mg resulted in dosedependent reductions (improvements) from baseline to end-oftreatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p≤0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p<0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events. Conclusions The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program

Considering how athletic identity assists adjustment to spinal cord injury: a qualitative study

Objectives: To establish how sport, and access to an athletic identity, has been used when adjusting to a spinal cord injury. Design: Qualitative study using semi-structured interviews. Setting: Private athletic club. Participants: Eight (six males and two females) athletes from a wheelchair badminton club participated in the study. The individuals had finished rehabilitation, and were aged between 20 and 50 years. Main outcome measures: A single semi-structured interview was undertaken with each participant. Results: Following the thematic analysis, two final themes were presented: (1) adjustment and paradox of chronic illness; and (2) the role and value of an athletic identity. Conclusions: Badminton provided participants with an opportunity to continue and develop a positive athletic identity. Identity may be used as a factor that can promote recovery, and is considered as a way to encourage and maintain positive long-term adjustment to disability