The role of botulinum toxin in the management of nonneurogenic overactive bladder in children: Highlights for clinical practice. A systematic review.

Overactive bladder (OAB) is the most common voiding dysfunction in children; however, nonneurogenic or idiopathic OAB remains poorly studied. First-line treatment includes conservative measures; however, as many patients are refractory, have adverse effects, or are contraindicated for anticholinergics, new options must be explored. This review covers the use of intravesical botulinum toxin (BoNT) for idiopathic OAB treatment in children, emphasizing its efficacy, safety, differences between toxins, doses, and injection techniques. Clinical results were promising, with all 8 studies reporting good results. All authors used BoNT type A (BoNT-A), either onabotulinum or abobotulinum toxin A. Response rates were variable, with full-response percentages of 32%-60%. As proven by the full-response rates of 50%, repeated injections are as safe and effective as first injections. Only a few cases of urinary tract infection, transient urinary retention, and hematuria have been reported, with no major local or systemic adverse effects. Despite these limitations, evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric settings, regardless of dosage and target toxin. To the best of our knowledge, this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Early endoscopic injection may prevent new scarring in idiopathic detrusor overactivity disorder with vesicoureteral reflux in children.

OBJECTIVE: To present baseline characteristics and the long-term treatment results of three groups of patients with idiopathic detrusor overactivity (IDOD) and vesicoureteral reflux (VUR) according to different treatment regimens, which underwent endoscopic subureteric injection (STING) in the early phase of targeted treatment (TT) (ES group), underwent STING in the late phase of TT (LS group) and with TT only (TT group). PATIENTS AND METHODS: A total of 49 IDOD cases with VUR which were divided into three groups according to treatment regimens were evaluated in terms of age, symptoms, bladder capacities, involuntary contraction pressures (ICP), presence and degree of renal scar, differential renal functions (DF), new scar formation and STING success. RESULTS: There was no significant difference between the groups in terms of age, side, symptoms, presence of urinary tract infection (UTI), DF, ICP and bladder capacity at diagnosis. A high grade of reflux was found to be significantly lower in the TT group (p = 0.037). There was no significant difference in terms of ICP, DF, bladder capacity and reflux grade between ES and LS Group. But new scar formation was more in LS Group (p = 0.003). CONCLUSION: The STING success is satisfactory in IDOD cases with VUR, waiting a long period of time for diminishing symptoms may cost new scar formation.

Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis.

Objective: Overactive bladder (OAB) is a disease characterized by the presence of urinary urgency. We carried out a meta-analysis to assess the effectiveness and safety of trigonal-involved injection of onabotulinumtoxinA (BoNT-A) in comparison with the trigonal-sparing technique in cases with OAB [neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO)]. Methods: Randomized controlled trials (RCTs) of BoNT-A injection for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The datum was calculated by RevMan version 5.3.0. The original references of relating articles were also reviewed. Results: In total, six RCTs involving 437 patients were included in our analysis. For OAB, the trigone-including group showed a different patient symptom score (p = 0.03), complete dryness rate (p = 0.002), frequency of incontinence episodes (p = 0.01), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.0004) compared with the trigone-sparing group. Also, a trigone-including intradetrusor injection demonstrated a significant improvement in the patient symptom score (p = 0.0004), complete dryness rate (p = 0.0002), frequency of incontinence episodes (p = 0.0003), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.00006) compared with the trigone-sparing group for treatment of NDO. The adverse events rates were similar in both groups. Conclusions: The meta-analysis has demonstrated that trigone-including BoNT-A injection was more effective compared with the trigone-sparing injection for the treatment of OAB, especially for NDO.

Objective and subjective improvement in children with idiopathic detrusor overactivity after intravesical botulinum toxin injection: A preliminary report.

OBJECTIVE: The purpose of this study is to evaluate the effect of Intravesical Botulinum toxin injection on the symptoms and urodynamic parameters in pediatric patients with idiopathic overactive bladder (iOAB) refractory to medical treatment. MATERIALS AND METHODS: The study was designed as an open-label uncontrolled therapeutic clinical trial. The eligible patients who underwent Intravesical botulinum toxin injection were evaluated before treatment. The evaluation included a 7-day paper bladder diary to assess OAB symptoms (frequency, urgency urinary incontinence (UUI) and nocturnal enuresis (NE)), filling the Arabic International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI short form), and conducting urodynamic study. The Urodynamic parameters obtained were the maximum filling detrusor pressure, cystometric bladder capacity, and compliance. After 12 weeks of the intravesical injection, the patients were revaluated and the results were compared using paired samples t-test. RESULTS: The study enrolled 75 patients. And of those, statistical analysis was done on 46 patients who did follow the study protocols. The mean age was 8.9 years and male to female ratio was 1:4. There was a statistically significant improvement in overactive bladder symptoms and urodynamic parameters in the patient injected with botulinum toxin with minimal side effects. CONCLUSION: The evidence in this study would support the safety and efficacy of Intravesical botulinum toxin injection in children with refractory idiopathic OAB with significant improvement of symptoms, quality of life, as well as urodynamic parameters. TYPE OF STUDY: Open-label uncontrolled therapeutic clinical trial. LEVEL OF EVIDENCE: III.

What is the true catheterization rate after intravesical onabotulinumtoxinA injection?

INTRODUCTION AND HYPOTHESIS: A known side effect of intravesical onabotulinumtoxinA (Botox®) injection for overactive bladder (OAB) is urinary retention requiring clean intermittent catheterization (CIC), the fear of which deters patients from choosing this therapy. In clinical practice, patients with an elevated postvoid residual (PVR) are often managed by observation only, providing they do not have subjective complaints or contraindications. We sought to determine the true rate of urinary retention requiring CIC in clinical practice. METHODS: A retrospective review was performed over a 3-year period of patients who received 100 units of intravesical onabotulinumtoxinA for the treatment of OAB. Patients were seen 2 weeks after the procedure to measure PVR. CIC was initiated in patients with a PVR ≥350 ml and in those with subjective voiding difficulty or acute retention. RESULTS: A total of 187 injections were performed on 99 female patients. CIC was required following three injections (1.6%): for acute retention in two patients and subjective voiding difficulty in one patient with a PVR of 353 ml. Following 12 injections, the patient had a PVR of ≥350 ml, and following 29 injections, the patient had a PVR of >200 but <350 ml without symptoms. CIC was not initiated in these 41 patients. None of these patients experienced subsequent retention, and all showed resolution of their elevated PVR within 8 weeks. CONCLUSIONS: In our series of 187 intravesical injections for OAB, the rate of postprocedure urinary retention requiring catheterization was only 1.6%. This low rate can be attributed to less rigorous criteria for CIC initiation than those applied in previous studies. While important to counsel patients on the risk of retention, patients can be reassured that the actual rate of CIC is low.

Expressions of urothelial functional proteins in idiopathic detrusor overactivity patients refractory to antimuscarinic therapy with different urodynamic characteristics.

AIMS: This study investigated the expressions of PGP9.5, P2 X 3 , muscarinic receptor (M3) and beta-3 adrenoreceptor (AR) in idiopathic detrusor overactivity (IDO) patients refractory to antimuscarinic treatment, and analyzed the correlation between protein expressions and clinical symptoms of IDO bladders with different urodynamic characteristics. METHODS: Specimens of 48 IDO and 10 control patients without lower urinary tract symptoms were included. The levels of these proteins from bladder mucosa were determined by Western blotting. RESULTS: The expression levels of ß3-AR and M3 receptor were similar between IDO patients and controls. When IDO patients were divided into two subgroups, phasic DO and terminal DO, the results showed that ß3-AR level in the patients with phasic DO was significantly higher than that of the controls and terminal DO (Both P < 0.05). PGP9.5 and P2 X 3 levels were also significantly increased in phasic DO subgroup than controls. P2 X 3 receptor was positively correlated with PGP9.5 and ß3-AR, and negatively correlated with the first sensation of bladder filling and voided volume in phasic DO. CONCLUSIONS: Similar expression M3 receptor and increased P2 X 3 levels in phasic DO, compared with the controls, indicate that dysregulation of purinergic bladder signaling may contribute to the pathogenesis of phasic DO refractory to antimuscarinics. Elevated expression of ß3-AR in phasic DO but not in terminal DO patients may explain the different urodynamic characteristics of DO between the two subgroups. Our findings suggest that ß3-AR agonist or P2 X 3 antagonist might be a good treatment choice for patients with phasic DO refractory to antimuscarinic therapy.

Overactive bladder in women.

Overactive bladder in women is a common chronic condition of urinary storage, affecting a significant proportion of the population. It is defined as a symptom diagnosis that indicates lower urinary tract dysfunction, in which patients experience urinary urgency, with or without urge incontinence, usually accompanied by frequency and nocturia. The diagnosis and treatment of overactive bladder are straightforward and systematic in line with national and international guidelines. However, women are required to disclose their bladder symptoms, and be motivated to make changes to their lifestyle to see improvements. This article focuses specifically on idiopathic detrusor overactivity; its diagnosis, treatment and psychological effects on women. Healthcare professionals require an understanding of the pathophysiology and treatment rationale for the condition to ensure appropriate management strategies for patients presenting to primary and secondary care are implemented.

[High doses of trospium chloride in patients with idiopathic overactive bladder. Data of large-scale, multicenter observational program Resource].

PURPOSE: Evaluation of the efficacy and safety of different doses of trospium chloride in patients with idiopathic overactive bladder. MATERIALS AND METHODS: Large-scale observational program "Resource" included 669 patients with idiopathic OAB - 359 women and 310 men. At the first visit, all patients were assigned to use of trospium chloride at a standard dose of 45 mg per day. The results of treatment were evaluated during follow-up visits at 3, 6, 9 and 12 weeks. Depending on the results of examination, the dose was reduced in the presence of adverse events and increased in case of insufficient treatment effects. RESULTS: After 12 weeks, 102 patients have been receiving the drug at a dose of 30 mg/day, 241 - at a dose of 45 mg/day, 257 - at a dose of 60 mg/day, and 22 - at a dose of 75 mg/day. CONCLUSIONS: Individual approach to the selection of doses of trospium chloride in patients with idiopathic OAB can be quite effective and safe measure to achieve optimal clinical outcome with a good safety profile.

Relationship between urodynamic patterns and lower urinary tract symptoms in Chinese women with a non-neurogenic bladder.

OBJECTIVE: To investigate the urodynamic study (UDS) patterns, obstruction status, continence status, and their correlations among neurologically intact women with lower urinary tract symptoms (LUTS) through an epidemiological and logistic regression analyses. METHODS: We retrospectively analyzed the UDS data of 3265 neurologically intact women with LUTS (2002-2014). Five UDS patterns were identified: normo-active detrusor/sphincter (NA, or DSI, detrusor/sphincter intact), idiopathic detrusor overactivity (IDO), idiopathic sphincter overactivity (ISO), IDO + ISO, and detrusor underactivity (DUA). Analyses of UDS pattern distribution and stratification were performed (based on a modification of the European Urological Association-Madersbacher classification system), and their correlations with bladder outlet obstruction (BOO) and stress urinary incontinence (SUI) status were evaluated via logistic regression analysis. RESULTS: NA, IDO, IDO + ISO, ISO, and DUA were noted in 927 (28.4%), 678 (20.8%), 320 (9.8%), 689 (21.1%), and 651 (19.9%) cases, respectively. Moreover, storage, storage + voiding, and voiding symptoms were noted in 62.4%, 21.1%, and 16.5% cases, respectively, whereas BOO and SUI were observed in 12.1% and 29.0% cases, respectively. The risk factors for BOO included NA, IDO, ISO, and IDO + ISO, whereas the protective factors against BOO included storage symptoms, SUI, storage + voiding symptoms, and complaint duration within 1-12 months. NA was the only risk factor for SUI, whereas BOO, storage + voiding symptoms, IDO, and storage symptoms were protective factors for SUI. CONCLUSION: Five UDS patterns were identified among neurologically intact women with LUTS. Functional abnormalities of the detrusor and/or sphincter were the main causes of LUTS, and were correlated with the BOO or SUI status. Thus, the UDS pattern can provide additional information regarding the risk factors for BOO or SUI status, as compared to symptomatic typing.

What is the feasibility of switching to 200IU OnabotulinumtoxinA in patients with detrusor overactivity who have previously received 300IU?

INTRODUCTION: To assess the feasibility of converting from 300IU to 200IU OnabotulinumtoxinA in patients diagnosed with either idiopathic detrusor overactivity (IDO) or neurogenic detrusor overactivity (NDO). MATERIAL AND METHODS: Retrospective case-notes review of patients who were converted from 300IU to 200IU OnabotulinumtoxinA. Subjective patient reported improvements at interview and bladder diary reported parameters of urgency, urgency incontinence, frequency and nocturia. RESULTS: Forty-four patients had received 300IU OnabotulinumtoxinA and were switched to 200IU after July 2008, 28 for IDO and 16 for NDO. Thirty-seven patients reported ongoing improvement with 200IU OnabotulinumtoxinA, six patients had worsening in their symptoms since down-titrating to 200IU and one patient did not attend follow-up. Improvement in urgency and urgency incontinence episodes per day were 82% and 72%, respectively, in patients who received 200IU. Of the 44 patients, 39 continued to receive 200IU, four requested up-titration to 300IU (due to decreased effect) and one did not attend after the 1st treatment. After converting from 300IU to 200IU, additional three patients were started on CISC for de novo voiding difficulty. CONCLUSIONS: Seventy-nine percent of patients were satisfied with their symptoms after switching from 300IU to 200IU OnabotulinumtoxinA. Only 9% of patients (all with NDO) reverted back to receiving 300IU. This study showed similar efficacy and longevity in the majority of patients (90%) using 200IU in both NDO and IDO.

An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders.

CONTEXT: Botulinum toxin A (BoNTA) has received regulatory approval for use in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), but it remains unlicensed in other lower urinary tract symptoms (LUTS) indications such as nonneurogenic LUTS in men with benign prostatic enlargement (LUTS/BPE), bladder pain syndrome (BPS), and detrusor sphincter dyssynergia (DSD). OBJECTIVE: To compare statistically the outcomes of high level of evidence (LE) studies with placebo using BoNTA for LUTS indications; NDO, OAB, LUTS/BPE, BPS and DSD. EVIDENCE ACQUISITION: We conducted a systematic review of the published literature on PubMed, Scopus, and Embase reporting on BoNTA use in LUTS dysfunction. Statistical comparison was made between high LE studies with placebo and low LE studies. EVIDENCE SYNTHESIS: In adult NDO, there are significantly greater improvements with BoNTA in daily incontinence and catheterisation episodes (-63% and -18%, respectively; p<0.01), and the urodynamic parameters of maximum cystometric capacity (MCC), reflex volume, and maximum detrusor pressure (MDP) (68%, 61%, and -42%, respectively; all p<0.01). In OAB, BoNTA leads to significant improvements in bladder diary parameters such as daily frequency (-29%), daily urgency (-38%), and daily incontinence (-59%) (all p<0.02). The urodynamic parameters of MCC and MDP improved by 58% (p=0.04) and -29% (p=0.002), respectively. The risk of urinary tract infection was significantly increased from placebo at 21% versus 7% (p<0.001), respectively; the risk of intermittent self-catherisation increased from 0% to 12% (p<0.001). Men with LUTS/BPE showed no significant improvements in International Prostate Symptom Score, maximum flow rate, or prostate volume. There were insufficient data for statistical analysis in DSD, BPS, and paediatric studies. Low LE studies were found to overestimate the effects of BoNTA in all indications, but differences from high LE studies were significant in only a few parameters. CONCLUSIONS: BoNTA significantly improves all symptoms and urodynamic parameters in NDO and OAB. The effect of BoNTA in treating LUTS dysfunction appears to be overestimated in lower as opposed to higher LE studies.

Sacral neuromodulation in patients with idiopathic overactive bladder after initial botulinum toxin therapy.

PURPOSE: We evaluated whether patients with overactive bladder and incontinence who discontinued intravesical botulinum toxin therapy can be successfully treated with sacral neuromodulation. MATERIALS AND METHODS: All patients who were referred to our center after discontinuation of botulinum toxin-A between 2005 and 2010 were included in this observational study. All patients underwent test stimulation with sacral neuromodulation and were evaluated with voiding diaries. Success was defined as more than 50% improvement in leakage episodes. Successful test stimulation was subsequently followed by a definitive implant. Patient satisfaction with sacral neuromodulation therapy was evaluated 1 year after the definitive implant. RESULTS: A total of 20 patients were included in the study. Of these patients 17 (85%) had discontinued botulinum toxin-A because of lack of efficacy and 3 had been treated successfully with botulinum toxin-A but requested a more permanent solution. The mean interval between the botulinum toxin-A and the sacral neuromodulation test stimulation was 23 months. In 14 patients (70%) the test stimulation was successful and they received a definitive implant. Of the 14 patients 5 even showed a decrease of greater than 90% in leakage episodes. One year after implantation 11 patients (79%) were satisfied with the sacral neuromodulation treatment. CONCLUSIONS: Despite the small sample size, this study indicates that patients who are dissatisfied with or in whom botulinum toxin-A treatment fails can respond successfully to sacral neuromodulation. The success rate of the test stimulation was comparable to that of patients who have never been treated with botulinum toxin-A. The 1-year satisfaction rate was comparable that of patients without a history of botulinum toxin-A treatment.

The use of botulinum toxin for the treatment of overactive bladder syndrome.

Over the last 50 years, botulinum toxin has been transformed from a cause of life-threatening disease to an effective medical therapy. It has been used in a variety of specialties for different indications, significantly improving patient quality of life. A recent growing body of evidence suggests that intra-detrusor injection of botulinum toxin may have beneficial effects in patients with medication refractory detrusor overactivity and may offer a new minimally invasive alternative to patients with severe overactive bladder symptoms. To review current data regarding the effects of botulinum toxin in patients with overactive bladder, a MEDLINE(®)/PubMed(®) literature search was carried out. The mechanism of action, clinical usage, adverse effects, and treatment efficacy were reviewed and the results are presented in this paper.

Dysfunctional elimination syndromes--how closely linked are constipation and encopresis with specific lower urinary tract conditions?

PURPOSE: It is recognized that there is a strong association between bladder and bowel dysfunction. We determined the association of constipation and/or encopresis with specific lower urinary tract conditions. MATERIALS AND METHODS: We reviewed our database of children with lower urinary tract dysfunction and divided cases into 3 categories of bowel dysfunction (constipation, encopresis and constipation plus encopresis) and 4 lower urinary tract conditions (dysfunctional voiding, idiopathic detrusor overactivity disorder, detrusor underutilization disorder and primary bladder neck dysfunction). Associations between bowel dysfunction types and each lower urinary tract condition were determined. RESULTS: Of 163 males and 205 females with a mean age of 8.5 years constipation was the most common bowel dysfunction (27%). Although encopresis is generally thought to reflect underlying constipation, only half of children with encopresis in this series had constipation. Dysfunctional voiding was associated with the highest incidence of bowel dysfunction. All but 1 patient with encopresis had associated urgency and detrusor overactivity, and the encopresis resolved in 75% of patients after initiation of anticholinergic therapy. Constipation was significantly more common in girls (27%) than in boys (11%, p <0.01), while encopresis was more common in boys (9%) than in girls (3%, p = 0.02), likely reflecting the higher incidence of dysfunctional voiding in girls and idiopathic detrusor overactivity disorder in boys. CONCLUSIONS: Active bowel dysfunction was seen in half of the children with a lower urinary tract condition. Constipation was more common in patients with dysfunctional voiding, while encopresis was significantly increased in those with idiopathic detrusor overactivity disorder and in those with dysfunctional voiding, severe urgency and detrusor overactivity. Anticholinergics, despite their constipating effect, given for treatment of detrusor overactivity resolved encopresis in most children with this bowel dysfunction.

Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction.

PURPOSE: There is a known association between nonneurogenic lower urinary tract conditions and vesicoureteral reflux. Whether reflux is secondary to the lower urinary tract condition or coincidental is controversial. We determined the rate of reflux resolution in patients with lower urinary tract dysfunction using targeted treatment for the underlying condition. MATERIALS AND METHODS: Patients diagnosed and treated for a lower urinary tract condition who had concomitant vesicoureteral reflux at or near the time of diagnosis were included. Patients underwent targeted treatment and antibiotic prophylaxis, and reflux was monitored with voiding cystourethrography or videourodynamics. RESULTS: Vesicoureteral reflux was identified in 58 ureters in 36 females and 5 males with a mean age of 6.2 years. After a mean of 3.1 years of treatment reflux resolved with targeted treatment in 26 of 58 ureters (45%). All of these patients had a history of urinary tract infections before starting targeted treatment. Resolution rates of vesicoureteral reflux were similar for all reflux grades. Resolution or significant improvement of reflux was greater in the ureters of patients with dysfunctional voiding (70%) compared to those with idiopathic detrusor overactivity disorder (38%) or detrusor underutilization (40%). CONCLUSIONS: Vesicoureteral reflux associated with lower urinary tract conditions resolved with targeted treatment and antibiotic prophylaxis in 45% of ureters. Unlike the resolution rates reported in patients with reflux without a coexisting lower urinary tract condition, we found that there were no differences in resolution rates among grades I to V reflux in patients with lower urinary tract conditions. Patients with dysfunctional voiding had the most improvement and greatest resolution of reflux. Additionally grade V reflux resolved in some patients.

Prevalence of urinary tract infection and vesicoureteral reflux in children with lower urinary tract dysfunction.

PURPOSE: Lower urinary tract dysfunction is a common pediatric urological problem that is often associated with urinary tract infection. We determined the prevalence of a urinary tract infection history in children with lower urinary tract dysfunction and its association, if any, with gender, bowel dysfunction, vesicoureteral reflux and specific lower urinary tract conditions. MATERIALS AND METHODS: We retrospectively reviewed the charts of children diagnosed with and treated for lower urinary tract dysfunction, noting a history of urinary tract infection with or without fever, gender, bowel dysfunction and vesicoureteral reflux in association with specific lower urinary tract conditions. RESULTS: Of the 257 boys and 366 girls with a mean age of 9.1 years 207 (33%) had a urinary tract infection history, including 88 with at least 1 febrile infection. A total of 64 patients underwent voiding cystourethrogram/videourodynamics, which revealed reflux in 44 (69%). In 119 of the 207 patients all infections were afebrile and 18 underwent voiding cystourethrogram/videourodynamics, which revealed reflux in 5 (28%). A urinary tract infection history was noted in 53% of girls but only 5% of boys (p <0.001). Patients with detrusor underutilization disorder were statistically more likely to present with an infection history than patients with idiopathic detrusor overactivity disorder or primary bladder neck dysfunction (each p <0.01). CONCLUSIONS: Females with lower urinary tract dysfunction have a much higher urinary tract infection incidence than males. This association was most often noted for lower urinary tract conditions in which urinary stasis occurs, including detrusor underutilization disorder and dysfunctional voiding. Reflux was found in most girls with a history of febrile infections. Since reflux was identified in more than a quarter of girls with only afebrile infections who were evaluated for reflux, it may be reasonable to perform voiding cystourethrogram or videourodynamics in some of them to identify reflux.

Botulinum toxin-A for the treatment of overactive bladder: UK contributions.

BACKGROUND: Botulinum toxin-A (BoNT/A) is now established second-line management for refractory overactive bladder (OAB) and recognised in many incontinence guidelines and pathways. For those with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis, the toxin is currently licensed in certain parts of the world, including the UK. It is an effective treatment in those in whom antimuscarinics and conservative measures have failed who have symptoms of OAB and or detrusor overactivity (DO). METHODS: Treatment can be given in an outpatient setting and can be administered under local anaesthesia. Its efficacy lasts for between six and 12 months. RESULTS: It has an acceptable safety profile with the biggest risk being urinary tract infection and difficulty emptying the bladder, necessitating clean intermittent self-catheterisation (CISC). Medium-term follow-up suggests repeated injections are also safe and efficacious. CONCLUSIONS: The mechanism of action of the toxin is more complicated than originally thought, and it seems likely that it affects motor and sensory nerves of the bladder. In the last 10 years much of the progress of this treatment from early experimental trials to mainstream clinical use, and a better understanding of how it works in the bladder, are as a result of research conducted in the UK. This review summarises the significant and substantial evidence for BoNT/A to treat refractory OAB from UK centres.