Intravesical Botulinum Toxin A Research Articles

Impact of intravesical onabotulinumtoxinA on sexual function in women with OAB.

Urgency urinary incontinence (UUI), and the symptoms of overactive bladder (OAB) have a negative impact on female sexual function. The aim of this study was to investigate the effect of intravesical onabotulinumtoxinA (Botox) injection on sexual function in women with OAB, using the multi domain Female Sexual Function Index (FSFI) questionnaire. Sixty-eight sexually active women with idiopathic OAB with at least one episode of UUI and ≥8 micturitions per 24 h were recruited. Patients completed the FSFI questionnaire before and 12 weeks after treatment with intravesical onabotulinumtoxinA injections. Baseline scores were compared with a control group of age-matched healthy women. Fifty-six women completed the study. At baseline OAB patients reported decreased quality of sexual function in all domains measured with FSFI, in comparison to healthy women (median 21.8 vs. 26.3, P < 0.001). Over 90% of participants reported clinically relevant improvements in sexual function, with statistically significant changes in mean scores in all six domains. Intravesical Botox injections provide improvement in sexual function in women with OAB. Neurourol. Urodynam. 9999:XX-XX, 2016. © 2016 Wiley Periodicals, Inc.

Intravesical Botulinum Toxin A Injections for Bladder Pain Syndrome/Interstitial Cystitis: A Systematic Review and Meta-Analysis of Controlled Studies.

BackgroundThe role of intravesical botulinum toxin A (BTX-A) injections in bladder pain syndrome/interstitial cystitis (BPS/IC) has not been clearly defined. The aim of this study was to evaluate high-level evidence regarding the efficacy and safety of BTX-A injections for BPS/IC.Material/MethodsWe conducted a comprehensive search of PubMed, Embase, and Web of Science, and conducted a systematic review and meta-analysis of all available randomized controlled trials (RCTs) and controlled studies assessing BTX-A injections for BPS/IC.ResultsSeven RCTs and 1 retrospective study were identified based on the selection criteria. Pooled analyses showed that although BTX-A was associated with a slightly larger volume of post-void residual urine (PVR) (weighted mean difference [WMD] 10.94 mL; 95% confidence intervals [CI] 3.32 to 18.56; p=0.005), patients in this group might benefit from greater reduction in pelvic pain (WMD −1.73; 95% CI −3.16 to −0.29; p=0.02), Interstitial Cystitis Problem Index (ICPI) scores (WMD −1.25; 95% CI −2.20 to −0.30; p=0.01), and Interstitial Cystitis Symptom Index (ICSI) scores (WMD −1.16; 95% CI −2.22 to −0.11; p=0.03), and significant improvement in daytime frequency of urination (WMD −2.36; 95% CI −4.23 to −0.49; p=0.01) and maximum cystometric capacity (MCC) (WMD 50.49 mL; 95% CI 25.27 to 75.71; p<0.00001). Nocturia, maximal urinary flow rate, dysuria, and urinary tract infection did not differ significantly between the 2 groups.ConclusionsIntravesical BTX-A injections might offer significant improvement in bladder pain symptoms, daytime urination frequency, and MCC for patients with refractory BPS/IC, with a slightly larger PVR. Further well-designed, large-scale RCTs are required to confirm the findings of this analysis.

Intravesical botulinum toxin-A: Does the injection template matter?

Objective: The efficacy of intravesical botulinum toxin-A (BTX-A) for the treatment of idiopathic detrusor overactivity (IDO) is well-established and evidence-based. The optimal regime in terms of dose, distribution, depth of injection and number of injections has not been determined and there is still considerable variation throughout clinical practice. We aim to establish the optimum template for bladder injections. Patients and methods: All patients had urodynamically-proven IDO which had failed conservative and medical management. AbobotulinumtoxinA (250 units) was injected into the detrusor and sub-urothelium in one of five injection templates under general anaesthetic. An Overactive Bladder Symptom Score (OABSS) and International Prostate Symptoms Score (IPSS)-Likert quality of life (QoL) score was completed pre-operatively and at six weeks post-operatively. In those who underwent repeat treatments the time to re-commencement of pharmacological therapy was recorded. Results: In total 111 patients received 170 treatments. The average age of patients was 57 (range: 17–86) and the male: female ratio was 0.18:1. Overall there was a mean improvement in the OABSS by −3.7 points±4.29 (standard deviation (SD) ( p&lt;0.01) and an average change in the QoL score of −2.18±2.17 (SD) ( p&lt;0.01) with BTX-A treatment. When analysed by template subgroup there was no statistically significant difference in the magnitude of change for any template over the other four for either the OABSS ( p=0.78) or QoL scores ( p=0.56). Forty-one patients had multiple treatments and had data collected for the duration to treatment failure. The overall average time to treatment failure was 11.2±7.9 months. Subgroup analysis showed that there was no statistically significant ( p=0.783) difference in time to treatment failure for any one of the injection distributions. Conclusion: This study has shown that altering the injection protocol of BTX-A did not affect the clinical outcome in terms of symptoms, QoL or in the time to treatment failure.

Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder symptoms.

Intravesical botulinum toxin (BoNT-A) is a safe and effective treatment for overactive bladder syndrome. There are many reports on the clinical experience with BoNT-A, especially in patients with neurogenic detrusor overactivity. The US Food and Drug Administration has recently approved its use for idiopathic overactive bladder (iOAB). Various studies have reported positive results for iOAB in the short-term. Yet little is known about the results after repeated BoNT-A injections. In this study, we evaluated the long-term results of botulinum toxin (BoNT-A) in women with iOAB. Patients treated with BoNT-A from 2004 until 2009 were evaluated in a non-academic teaching hospital (Zuyderland MC, Heerlen, the Netherlands). All female patients with a follow-up of >5years with idiopathic bladder dysfunction were included. All patients received 200U of onabotulinum toxin-A in 20 intradetrusor injections. In some patients, we applied a dose adjustment for repeated injections. Patients were instructed how to use clean intermittent self-catheterization (CISC) before the treatment. We advised patients to commence CISC if post-void residual exceeded 150ml. A total of 128 women were included. All patients had at least 5-year follow-up after their first injection. The mean follow-up was 97 (60-125) months. The mean age was 67 (46-88) years. Of all patients, 30% were still on BoNT-A treatment at the last follow-up visit. Of the 70% that discontinued treatment, 27% had insufficient effect and 43% had tolerability issues. Most patients discontinued treatment after the first (79%) and second (19%) injections. Only 2% of patients discontinued treatment after more than two injections during follow-up. Intravesical BoNT-A is an effective treatment for women with idiopathic OAB. However, in time, almost two-thirds of patients in our study discontinued therapy. Most patients discontinue treatment after one or two injections and mainly due to tolerability issues.

Can botox improve night-time overactive bladder symptoms in women?

Despite the efficacy of intravesical onabotulinumtoxinA (Botox) therapy for urgency, urgency incontinence, and daytime frequency, its value in treatment of nocturia remains unclear. The aim of the prospective observational study was to assess the effect of onabotulinumtoxinA on night-time symptoms in women with overactive bladder (OAB), including nocturia, night-time urgency incontinence, and nocturnal voided volume as end-points. Women with idiopathic OAB (with at least one episode of urgency urinary incontinence (UUI) per day, ≥8 micturitions per 24 hr, and ≥2 nocturia episodes per night) were enrolled. Patients with nocturnal polyuria were excluded. Botox (100 U) was administered in 20 intra-detrusor injections. Post-void residual volumes (PVR) were checked at 2, 4, and 12 weeks. Participants completed a 3-day bladder diary and the King's Health Questionnaire (KHQ) before and 12 weeks after treatment, and reported the efficacy of the treatment on visual analog scale (VAS) at the final follow-up visit. Seventy-six women completed the study. Botox injections were effective in the reduction of nocturia episodes (mean -0.98; P < 0.001) and night-time UUI episodes (-0.37; P < 0.001) compared to the baseline. The increase of mean voided volume of the night-time micturitions was 92.6 ml (P < 0.001). Patients reported a mean 58 points of improvement on the VAS. Urinary retention, which required self-catheterization, was observed in three patients. Intravesical Botox injection provides significant benefit for night-time symptoms in OAB patients. Our results are applicable for women without nocturnal polyuria, and should prove useful when counseling patients about the risks and benefits of Botox. Neurourol. Urodynam. 36:648-652, 2017. © 2016 Wiley Periodicals, Inc.

Clinical presentation and treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) in India.

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterized by pelvic pain urgency and frequency. Patients with severe symptoms lead a very miserable life. North American, European and Asian guidelines have been recently promulgated but they differ on many important issues. There is no consensus on its name, definition, investigations and management. Indian guidelines have also been developed and they give more importance to the symptoms in relation to micturition. Though initially believed to be rare or non-existent in India the situation has changed. In Indian patients the presentation is more or less same as the rest of the world but a large percentage have obstructive symptoms and unusual urinary symptoms. Anal discomfort is also common. In India the commonest investigation in all cases of lower urinary tract (LUT) dysfunction is ultrasonography of kidney ureter and bladder with measurement of the post void residual urine volume. Cystoscopy is also done in all the cases to rule out presence of tuberculosis or carcinoma in situ. Bladder pain syndrome/interstitial cystitis (BPS/IC) is not considered to be a clinical disease as it is difficult to rule out all differential diagnosis only from history. Hunner’s lesion is very rare. Cystoscopy with hydro distension, oral therapy, intravesical therapy and surgical therapy form the back bone of management. It is difficult to know which treatment is best for a given patient. A staged protocol is followed and all the treatment modalities are applied to the patients in a sequential fashion—starting from the non-invasive to more invasive. Intravesical botox has not been found to be effective and there is no experience with interstim neuromodulation.

Ten years of experience with intravesical and intrasphincteric onabotulinumtoxinA in children

To review 10 years of experience with both intravesical and intrasphincteric onabotulinumtoxinA (Botox(®)) injections in children. Fifty three children aged between 1 and 18 years at first injection had a combined total of 134 injections (106 intravesical, 23 intrasphincteric and five combined) between January 2004 and December 2013 at Princess Margaret Hospital. Follow-up occurred 3 months post procedure, and then 3-6 monthly. Response to Botox was graded according to the International Children's Continence Society (ICCS) response to treatment scale. Response time was the time that the injection remained effective before symptoms relapsed to the ICCS 'no response' category Nevéus etal., 2006. Median response times to Botox by pathology are summarised in Table 1. For detrusor overactivity (DO), the response after each Botox injection was in the ICCS '>90% symptom reduction' category Nevéus etal., 2006. Two children had sustained responses to Botox for a tenth and eleventh injection, respectively. A total of 45% of children receiving intrasphincteric Botox for chronic dysfunctional voiding (DV) or detrusor sphincter dyssynergia (DSD) had no symptom recurrence. Intravesical Botox was effective for treating new-onset hydronephrosis secondary to neurogenic bladder in one child. Intravesical Botox had a sustained effect over five injections in eliminating trigonal hypersensitivity and pain with CIC in one child. Episodes of severe autonomic dysreflexia in one child with a high cord transection were effectively eliminated by intravesical Botox, and were sustained over three injections. Thirteen of the 134 Botox injections (9.7%) had a symptomatic culture-positive urinary tract infection (UTI) in the 2 weeks following injection. All had a history of previous UTI. Three children (2.8%) developed urinary retention after intravesical injection. Intravesical Botox remained effective after up to eleven injections. In children with DV or DSD, the response to Botox was more variable, but 45% experienced symptom resolution with no recurrence. Trigonal hypersensitivity with CIC improved in a child after Botox. Botox may confer long-term bladder and upper tract protection in the neurogenic patient group. Severe episodes of autonomic dysreflexia triggered by bladder fill in a child with high cord lesion were eliminated by intravesical Botox. This study demonstrated that intravesical Botox remained effective in response quality and response time in children up to an eleventh injection. This is one of the longer follow-up studies in children published to date. Botox was effective in numbing trigonal hypersensitivity, treating new-onset hydronephrosis secondary to neurogenic bladder, and eliminating episodes of autonomic dysreflexia in one patient each.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months’ duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

Intravesical botulinum toxin-a injections reduce bladder pain of interstitial cystitis/ bladder pain syndrome refractory to conventional treatment – a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial

Intravesical botulinum toxin-a injections reduce bladder pain of interstitial cystitis/ bladder pain syndrome refractory to conventional treatment – a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial

150 Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder syndrome

150 Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder syndrome

Results of intravesical botulinum toxin A in men with idiopathic overactive bladder symptoms

Objective: The objective of this article is to determine treatment outcomes and risk factors for urinary retention in men with idiopathic overactive bladder (OAB) symptoms treated with intravesical botulinum toxin A (BTXA). Patients and methods: All men undergoing intravesical BTXA treatment from 2009 to 2013 at the Royal Berkshire Hospital were identified. Pre-treatment urodynamics and outcomes of treatment were determined. Results: A total of 35/43 men were deemed to have idiopathic OAB. Symptomatic improvement was seen in six of 13 (46%) dry OAB and 12/22 (55%) wet OAB irrespective of proven detrusor overactivity. Catheterisation rates were dose dependent with an overall rate of 16/35 (46%). Four of nine (44%) with bladder outflow obstruction required catheterisation, as did eight of 17 (47%) without. Twelve of 25 (48%) men with a Bladder Contractility Index (BCI) ⩽120 required catheterisation, as did four of 10 (40%) with a BCI &gt;120. Conclusion: BTXA is a successful treatment in males with idiopathic wet and dry OAB, irrespective of detrusor overactivity. One hundred units is an appropriate dose at which to begin treatment. Surprisingly, presence of bladder outflow obstruction and weak bladder contractility did not demonstrate an increased risk for catheterisation although further study should be conducted with larger numbers of patients.

Botulinum Toxin A Injections for Non-neurogenic Overactive Bladder

Intravesical botulinum toxin A (BoNT-A) injection is effective and has been approved in the treatment of overactive bladder (OAB) syndrome in patients who are refractory or intolerable to antimuscarinic therapy. Intravesical BoNT-A injection increases bladder capacity, decreases detrusor pressure, and reduces the urgency sensation in OAB patients. Although clinical experiences have demonstrated a dose-dependent therapeutic effect of BoNT-A, the adverse events such as acute urinary retention, voiding difficulty, large post-void residual, and subsequent urinary tract infection remain problematic and increase with higher doses in frail elderly patients. Currently, 100 U of onabotulinumtoxinA has been approved by many countries for the treatment of patients with non-neurogenic OAB. The duration of therapeutic effect is around 6 to 9 months and usually remains the same after repeat treatments. The injection sites can involve the bladder wall with or without sparing the trigone. Gathered experience has also shown that BoNT-A injection is also effective in the treatment of OAB symptoms in children and in patients with stroke or Parkinson’s disease. Before BoNT-A injection, physicians should learn the injection technique and inform the potential adverse events to patients who desire this treatment.

Interstitial Cystitis / Painful Bladder Syndrome (IC/PBS) Dilemmas in Diagnosis &amp; Treatment

Interstitial Cystitis/Painful Bladder Syndrome is a controversial chronic disease characterized by pain, urgency and frequency. Patients with severe symptoms have a very miserable life. There is still no international consensus on its name, definition, investigations and management. American, European and Asian guidelines have been recently framed but differ on many important issues. Presentations of IC/PBS patients are highly individual with the same or similar symptoms expressed differently. However, an important aspect of the symptoms is their relation to micturition. Since no internationally accepted standards exist for diagnosis and treatment, considerable variation is observed in the patient investigations. Investigations are divided between mandatory and optional. Sonography of kidney-ureter-bladder and urine culture are mandatory investigations as they rule out other pathologies. However, there is no consensus on important investigations such as cystoscopy. Some urologists believe painful bladder syndrome to be a clinical disease diagnosed on the basis of history and minimum investigations, while according to others cystoscopy confirms the disease by ruling out other potential causes of the symptoms and also helps in management decision-making. No standard protocol exists for treatment. All the available treatments work on a few patients and it is difficult to decide which treatment is best for a given patient. This dilemma has led to a policy of staged treatment where various treatment modalities are applied to the patient one after other, starting with less invasive and progressing to more invasive. Some treatment modalities like intravesical Botox and neuro-modulation are for patients with refractory IC/PBS only. Keywords: Guidelines, interstitial cystitis, mandatory investigations, painful bladder syndrome, refractory disease, staged treatment.

Intravesical Botulinum Toxin A Injections Do Not Benefit Patients with Ulcer Type Interstitial Cystitis

Background: Ulcer type and non-ulcer type interstitial cystitis/bladder pain syndromes (IC/BPS) are considered different disease entities. Thus, intravesical botulinum toxin A (BoNT-A) treatment outcomes could differ for each entity. Objectives: To evaluate and compare the treatment outcomes of BoNT-A injections for treatment of each IC/BPS type. Study Design: Prospective interventional study. Setting: Tertiary medical center affiliated with Buddhist Tzu Chi General Hospital and Tzu Chi University, Taiwan. Methods: Forty-four consecutive patients with IC/BPS for whom conventional treatments failed were prospectively enrolled in this study. Patients were classified as having ulcer (n = 10) or non-ulcer (n = 30) IC/BPS based on their previous cystoscopic findings. Intervention: All patients received 4 sets of intravesical BoNT-A injections (100 U in 40 suburothelial injections) every 6 months. The primary end-point was the global response assessment (GRA) 6 months after the fourth set of BoNT-A injections. Secondary end-points included the O’Leary-Sant score (OSS) including symptom indexes (ICSI) and problem indexes (ICPI), visual analog scale (VAS) pain score, voiding diary, and urodynamics variables. Results: After 4 sets of BoNT-A injections, 15 patients with non-ulcer IC/BPS had GRA scores ≥ 2, while the other 15 had GRA scores &lt; 2. All 10 patients with ulcer IC/BPS had GRA scores &lt; 2 at the study end-point (treatment failure). At baseline, patients with ulcer IC/BPS had significantly higher daytime frequency, nocturia, smaller functional bladder capacity, smaller voided volume, greater VAS, smaller maximal bladder capacity, and greater glomerulation grade than did patients with non-ulcer IC/BPS. After 4 sets of BoNT-A injections, patients with non-ulcer IC/BPS and GRA scores ≥ 2 or &lt; 2 all had significantly decreased ICSI, ICPI, OSS, VAS pain scores, frequency episodes, and increased functional bladder capacity. However, patients with ulcer IC/BPS showed no significant change in any clinical or urodynamic variable. After failure of repeated BoNT-A injections, all 10 patients with ulcer IC/ BPS underwent transurethral electrocauterization of their ulcers, which resulted in immediate pain relief. Limitations: Lack of a control arm in this study. Conclusion: Repeated intravesical BoNT-A injections provided effective treatment outcomes at the end-point in half of the patients with non-ulcer IC/BPS, but did not benefit any patient with ulcer type IC/BPS. Ulcer type IC/BPS should be treated as a different disease than non-ulcer IC/BPS. Institutional Review: This study was approved by the Institutional Review Board of the Tzu-chi General Hospital (TCGH 100-06). Key words: Botulinum toxin, interstitial cystitis, bladder pain syndrome, intravesical treatment, Hunner’s ulcer

Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A single set of botulinum toxin A (BoNT-A) injections relieves clinical symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks long-term effect. An inadequate anti-inflammatory effect is likely to cause treatment failure. The study shows that chronic inflammation and apoptotic signalling molecules are significantly reduced after repeated intravesical BoNT-A injection in patients with IC/BPS. It also shows that repeated BoNT-A injections are necessary to achieve greater success in the treatment of IC/BPS. To investigate the mechanisms of action of botulinum toxin A (BoNT-A) treatment on interstitial cystitis/bladder pain syndrome (IC/BPS). A total of 23 women with IC/BPS who received single intravesical BoNT-A injection were studied. Among them, 11 received three repeated injections every 6 months to improve their symptoms. Bladder biopsy was obtained before each BoNT-A injection and the clinical symptoms and urodynamic variables were recorded. Immunohistochemical (IHC) staining for TUNEL and mast cell activity, and western blotting analysis of tryptase, cytokines, Bax and phospho-p38 (p-p38) were carried out. We compared the clinical results and IHC data among baseline, single or repeated BoNT-A treatments. Single BoNT-A injection improved clinical symptoms, pain score and daytime urinary frequency. Mast cell activity and apoptotic cell count did not decrease significantly, while Bax and p-p38, but not tryptase, decreased significantly after a single BoNT-A injection. The 11 patients who received three repeated BoNT-A injections had significantly lower pain scores than the remaining patients (mean [SD]: 5.80 [2.27] vs. 3.03 [2.30], P = 0), glomerulation degree (mean [SD]: 1.80 [1.06] vs. 1.20 [1.06], P = 0.026) and global response scores (mean [SD]: 0.30 [0.92] vs. 1.20 [1.06], P = 0) after treatment. Tryptase, Bax, p-p38 and apoptotic cell counts all decreased significantly. 25-kD synaptosomal-associated protein also decreased after BoNT-A treatments, which confirmed the therapeutic effect of repeated BoNT-A injections. Chronic inflammation and apoptotic signalling molecules were significantly reduced after repeated BoNT-A injections in patients with IC/BPS. The IHC improvement was associated with clinical symptom improvement. Repeated BoNT-A injections are necessary to achieve a greater success rate in the treatment of IC/BPS.

113 DECREASE OF UROTHELIAL CELL APOPTOSIS SIGNAL MOLECULES IS ASSOCIATED WITH IMPROVEMENT OF CLINICAL SYMPTOMS AFTER SINGLE INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR PATIENTS WITH INTERSTITIAL CYSTITIS

INTRODUCTION AND OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) is considered to result from long-standing inflammation of bladder. Currently, no one treatment provides longterm efficacy. Intravesical botulinum toxin A (BoNT-A) injection seems to have promising therapeutic effect on IC/PBS. Several studies indicated that p38 MAPK activation is implicated in inflammation, fibrosis and mediating apoptosis in different cell types in various species. We have found that apoptosis of urothelial cells in IC/PBS could be due to up-regulation of inflammatory signals, including p38 MAPK and TNF . This study aimed to investigate whether the changes of bladder inflammation and apoptotic signal transduction could be modulated by intravesical BoNT-A injection in IC/PBS. METHODS: Twenty three patients with IC/PBS were enrolled. All patients received intravesical 100U BoNT-A injection. The bladder specimens were obtained at baseline and 6 months after the first injection. The double stain, protein array analysis and western blotting were performed to analyze the alterations of tryptase (mast cell activity), Bax, and phospho-p38 . The intensities of proteins in the arrays and Western blots were quantified using Image J processing. Inflammatory molecule treated urothelial cells were analyzed by TUNEL staining and western blotting for level of molecules involved in apoptosis. RESULTS: Clinical results after BoNT-A injection revealed improvement of visual analog score, O’Leary-Sant symptom score, and global response assessment but not glomerulation and maximal bladder capacity in overall patients (Table). Phospho-p38 and TUNEL double staining indicated that inflammatory and apoptotic events were co-existed in IC/PBS bladders. Analysis of the western blot results revealed significant decrease of phospho-p38 and Bax expression after the first time BoNT-A injection. However, the change of tryptase did not reach statistical significance. CONCLUSIONS: Single BoNT-A injection provides clinical improvement and reduce apoptotic signal protein production but mast cell activity did not significantly reduce, suggesting repeat BoNT-A injection is necessary to achieve long-term effect. Table. The changes of clinical measures and western blot measures parameters Baseline 6 months after BoNT-A P values VAS 5.30 2.46 3.78 2.61 0.048

Botulinum Toxin-A for the Treatment of Voiding Dysfunction: Our Initial Experience

Objective: Evaluation of Botulinum Toxin-A (BTX-A) as an alternative treatment option in patients whom previous treatments were failed. Methods: Between March 2005 and September 2006, a total 19 patients; 16 patients with overactive bladder (5 neurologic, 11 idiopathic), 2 with nocturnal enuresis, 1 with interstitial cystitis, intravesical BTX-A injection was applied. Except one patient, 18 patients with a median age 46 (20 - 80) were registered to the study. Patients were examined at postoperative 3 weeks and 6 months with ICIQ-SF (International Consultation on Incontinence Questionnaire-Short Form) and satisfaction forms used in our clinic. Results: The median follow-up time was 16 months (6 - 18). When evaluated according to diagnosis, symptoms were improved 100% in neurologic overactive bladder (5/5), 80% in idiopathic overactivity (8/10), 50% in nocturnal enuresis (1/2). In one patient with interstitial cystitis there was no improvement. Median efficiency time of BTX-A treatment was 6 months (1 - 17). At 3 weeks and 6 months after the treatment, ICIQ-SF score was decreased to 3.6 and 7.5 respectively from preoperative level of 18.7. Quality of life scores at preoperative, 3 week and 6 months were 9.7, 2.7 and 4.3 respectively. Except 3 patients with overactive neurologic bladder because of spinal cord injury, symptoms of patients with pollacuria and nocturia decreased at 3. week. Even if these rates increased at 6 months they still were significantly less than preoperative status. The spinal cord injured 3 patients had clean intermittent catheterization per 1 hour and had urinary incontinence between the catheterizations preoperatively, however at 3 weeks and 6 months the intervals of catheterisations was 4 hours and 3 hours respectively and also the urinary incontinance between the catheterisations improved. At patient satisfactions, 78% of patients declared that they were pleased and underwent the procedure again and will recommend it to their relatives with similar problems. One patient had a complication as tansient weakness on her legs. Conclusion: BTX-A injections provide an alternative treatment before surgery at overactive bladder especially for those who doesn’t response to medical treatment or cannot use antimuscarinics because of their side effects. Further studies with a greater number of patients are needed for determining the effectiveness of BTX-A on patients with voiding dysfunctions.

Central inhibitory effect of intravesically applied botulinum toxin A in chronic spinal cord injury

We evaluated a putative central inhibitory effect of intravesical botulinum toxin A (BoNT-A) on the activity of lumbosacral spinal neurons in a chronic spinal cord injury (SCI) model of bladder overactivity. Female Sprague-Dawley rats underwent T8 spinal cord transection. Four weeks later, once overactive neuropathic detrusor pathways had developed, the animals underwent intravesical instillation with either saline (1 ml) or BoNT-A (Botox®, 20 U/1 ml) for 1 hr. Two days later, the rats then completed a cystometric evaluation prior to spinal cord harvest. Sections from the L4-S1 spinal cord segments were examined for the total number of c-fos immunoreactive cells. Comparison of the saline and BoNT-A treated groups showed a significant decrease in L6 (i.e., 67%, P < 0.001) and S1 (i.e., 47%, P < 0.01) c-fos expression (43%) in BoNT-A treated rats compared to saline controls. Cystometrogram studies revealed that the frequency of non-voiding bladder contractions was reduced by 73% (P < 0.05) in BoNT-A compared to saline treated rats. No change in the frequency of voiding bladder contractions or amplitude of bladder contraction was observed between the saline and BoNT-A treated groups. In a SCI model of bladder overactivity, intravesical BoNT-A significantly inhibits the response of bladder afferent activated lumbosacral neurons without significantly impairing efferent bladder function.

The effectiveness of intravesical Botox in idiopathic and non-idiopathic detrusor over activity

Background and objectives: We have evaluated and compared the efficacy of Botox® in the treatment of bladder over activity in Idiopathic detrusor over activity (IDO) and Neuropathic detrusor over activity (NDO) in a tertiary centre. We hypothesised that the outcome of this less invasive treatment would be more promising in patients with IDO than those with NDO. Methods: A total of 229 patients were reviewed with overactive bladder proven by urodynamic studies over the last 2 years. Of these, 174 patients received Botox® injection. 132 (75%) patients had IDO and 42 (25%) patients had NDO. 200 IU of Botox® was injected per patient in the IDO group and 300 IU in the neurogenic group. Results: Eighty one of 118 (68.7%) known patients with IDO reported being dry after receiving the Botox® compared to 20/39 (51.3%) patients with NDO. Whereas, 88/118 (68.7%) patients with IDO reported significant satisfaction compared to 25/39 (64.1%) patients with NDO. Conclusion: Botox® is an effective, minimally invasive treatment for drug refractory IDO + NDO. In comparison, patient reported satisfaction and dryness with the procedure was statistically the same. However, the IDO group responded slightly better to treatment. The average mean effect was the same in both groups.

Intravesical botox for overactive bladder

Intravesical botox for overactive bladder