Intradetrusor Botulinum Toxin A Injections Research Articles

Role of Urological Botulinum Toxin-A Injection for Overactive Bladder and Voiding Dysfunction in Patients with Parkinson’s Disease or Post-Stroke

Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson's disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor overactivity (nDO) and then develop urinary incontinence and overactive bladder (OAB) symptoms. This study aimed to disclose the safety and efficacy of BoNT-A injection in treating bladder and voiding dysfunction in PD and post-stroke patients by reviewing the current evidence. At present, intradetrusor injection of BoNT-A is a Food and Drug Administration (FDA)-approved third-line therapy for nDO and idiopathic OAB. Although intradetrusor injection of onaBoNT-A 200 U is already approved for nDO treatment, most researchers would like to manage PD and post-stroke patients by using onaBoNT-A 100 U intradetrusor injection to achieve long-term efficacy and reduce adverse effects. However, in contrast to its inclusion in the International Continence Society guidelines for PD treatment, the clinical use of BoNT-A for post-stroke patients is limited to experimental use due to the development of urinary retention in about one-fifth of patients. For treating urethral pseudodyssynergia, half of patients may respond to onaBoNT-A 100 U urethral injection. However, refinement is needed to reduce unwanted urinary incontinence.

Functional Polymorphism in the ADRB3 Gene, Encoding the Beta-3 Adrenergic Receptor, and Response to Intra-Detrusor Injection of Botulinum Toxin-A in Women with Overactive Bladder.

There are reports suggesting an association between the rs4994 polymorphism in the ADRB3 gene encoding the beta-3 adrenergic receptor and OAB risk in females. The injection of botulinum toxin-A into the bladder wall is recommended as a possible treatment for OAB patients in whom first-line therapies have failed. The aim of our study was to analyze the possible association between the ADRB3:rs4994 polymorphism and the patient-perceived response to a single intra-detrusor injection of botulinum toxin-A in Polish women with overactive bladder. The study group consisted of 115 consecutive female patients with OAB. The response to botulinum toxin-A was evaluated at three months after injection, as absolute or relative reductions in OAB symptoms or in scores from questionnaires ICIQ-OAB (parts A and B) and ICIQ-LUTS-QoL (parts A and B). ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs. There were no statistically significant differences between ADRB3:rs4994 [T];[T] homozygotes and [T];[C]+[C];[C] subjects for absolute or relative reductions in symptoms or in scores from all four questionnaire parts at three months after the injection of botulinum toxin-A. Our results do not support the hypothesis that ADRB3:rs4994 polymorphism is associated with the response to the intra-detrusor injection of botulinum toxin-A in Polish females with overactive bladder.

PD36-05 URINARY MMP-2 IS SIGNIFICANTLY ASSOCIATED WITH THE RISK OF INTRADETRUSOR TOXIN INJECTIONS FAILURE IN PATIENTS WITH SPINA BIFIDA

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (PD36)1 Sep 2021PD36-05 URINARY MMP-2 IS SIGNIFICANTLY ASSOCIATED WITH THE RISK OF INTRADETRUSOR TOXIN INJECTIONS FAILURE IN PATIENTS WITH SPINA BIFIDA Benoit Peyronnet, Claire Richard, Claude Bendavid, Juliette Hascoet, Charlene Brochard, Magali Jezequel, Jacques Kerdraon, Emmanuelle Samson, Caroline Voiry, Guillaume Bouguen, Andrea Manunta, and Xavier Gamé Benoit PeyronnetBenoit Peyronnet More articles by this author , Claire RichardClaire Richard More articles by this author , Claude BendavidClaude Bendavid More articles by this author , Juliette HascoetJuliette Hascoet More articles by this author , Charlene BrochardCharlene Brochard More articles by this author , Magali JezequelMagali Jezequel More articles by this author , Jacques KerdraonJacques Kerdraon More articles by this author , Emmanuelle SamsonEmmanuelle Samson More articles by this author , Caroline VoiryCaroline Voiry More articles by this author , Guillaume BouguenGuillaume Bouguen More articles by this author , Andrea ManuntaAndrea Manunta More articles by this author , and Xavier GaméXavier Gamé More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002040.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Several studies have suggested that spina bifida patients may have a poorer response to intradetrusor botulinum toxin A (BTX-A) injections than other neurological populations without clear pathophysiological hypothesis to explain this finding. The objective of this study was to evaluate the association between intradetrusor BTX-A injection outcomes and the levels of six urinary biomarkers in spina bifida patients to investigate the possible mechanisms underpinning the poor response to BTX-A in this population. METHODS: A single center prospective study was conducted between March 2015 and March 2017 including all consecutive adult spina bifida patients who underwent intradetrusor BTX-A injection. At the end of the inclusion period, urines were defrosted and urinary NGF, BDNF, TIMP-2, TGF-B1 were assessed using validated ELISA kits. The urinary markers levels were adjusted on the urinary creatinine level. Urinary MMP-2 levels were assessed by zymography. The primary endpoint was the success of BTX-A injection defined as a combination of complete resolution of urinary incontinence and resolution of detrusor overactivity and or impaired bladder compliance on urodynamics 6 to 12 weeks after the injection. RESULTS: Twelve patients were included. The mean age was 38.1 years. The toxin used was onabotulinum toxin A in all cases at a dose of 200 U and 300 U in three and nine patients respectively. Four patients (33.3%) had a good clinical and urodynamic response to BTX-A and BTX-A intradetrusor injection failed clinically and or urodynamically in 8 patients(66.7%). Urinary MMP-2 levels were significantly higher in the failure group (1.30 vs. 0.44 ng/ml; p=0.04). Urinary TGF-B1/Cr and TIMP-2/Cr levels tended to be higher in the failure group (41.7 vs. 9.2 pg/mg of creatinine; p=0.31 and 479.5 vs. 345.1 pg/mg of creatinine; p=0.17). In contrast, urinary PGE2/Cr, NGF/Cr and BDNF/Cr levels did not vary with BTX-A response. CONCLUSIONS: Increased urinary MMP-2 level was associated with failure of intradetrusor BTX-A injections in spina bifida patients. Extracellular matrix remodelling with bladder wall fibrosis could therefore be the main cause of BTX-A injection failure in this population and points to a potential new therapeutic pathway for these patients. Source of Funding: chu rennesfondation de l'avenir © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e597-e597 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benoit Peyronnet More articles by this author Claire Richard More articles by this author Claude Bendavid More articles by this author Juliette Hascoet More articles by this author Charlene Brochard More articles by this author Magali Jezequel More articles by this author Jacques Kerdraon More articles by this author Emmanuelle Samson More articles by this author Caroline Voiry More articles by this author Guillaume Bouguen More articles by this author Andrea Manunta More articles by this author Xavier Gamé More articles by this author Expand All Advertisement Loading ...

Comparison of intravesical instillation of hyaluronic acid with intradetrusor botulinum toxin A injection or cystoscopic hydrodistention for ketamine-associated cystitis.

ObjectiveThis study aimed to compare the therapeutic effect of intravesical instillation hyaluronic acid with intradetrusor botulinum toxin A (BTX-A) injection or cystoscopic hydrodistention for ketamine-associated cystitis.MethodsThirty-six patients were evenly randomly divided into the BTX-A group or the hydrodistention group. Patients received 200 U BTX-A detrusor injections in the BTX-A group and cystoscopic hydrodistention in the hydrodistention group. Intravesical instillation of hyaluronic acid was administrated in both groups for eight times. Patients with involuntary detrusor contraction were divided into the persistent involuntary detrusor contraction group and resolved involuntary detrusor contraction group after treatment in 6 months. The predictors of persistent involuntary detrusor contraction were analyzed.ResultsTwelve months after treatment, the daytime frequency, Interstitial Cystitis Symptom Index, maximal capacity, and maximal cystometric capacity in the BTX-A group were significantly better than those in the hydrodistention group. Patients with resolution of involuntary detrusor contraction had a significantly shorter duration of ketamine, lower amount of fibrosis in pathology, and higher maximal capacity than those with persistent involuntary detrusor contraction 6 months after therapy.ConclusionIntravesical instillation of hyaluronic acid with intradetrusor BTX-A injection appears to be a preferable option for long-term effectiveness compared with cystoscopic hydrodistention.

Impact of intradetrusor botulinum toxin A injections on serum and urinary concentrations of nerve growth factor and brain-derived neurotrophic factor in patients with multiple sclerosis and neurogenic detrusor overactivity.

To evaluate the practical relevance of changes in serum and urinary neurotrophins levels in patients with multiple sclerosis (MS) and neurogenic lower urinary tract dysfunction (NLUTD) after intradetrusor injections of botulinum toxin A (BoNTA). The study included 36 patients with MS and NLUTD and 20 controls. The patients with NLUTD received intradetrusor injection of BoNTA (200 U). The nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were measured in serum and urine at baseline and then at 1, 3, and 6 months by enzyme-linked immunosorbent assay. Urinary NGF and BDNF were normalized to creatinine (NGF/Cr, BDNF/Cr). Patients' assessment included urodynamic examination and Neurogenic Bladder Symptom Score (NBSS). After BoNTA injections, no significant changes were observed in the serum NGF and BDNF or the urinary BDNF/Cr. The urinary NGF/Cr was significantly higher in MS patients (1.23 ± 0.34) at baseline compared with controls (0.084 ± 0.02; p = .021). The urinary NGF/Cr decreased to 0.51 ± 0.12 (p = .001) and 0.53 ± 0.32 (p = .005) at 1 and 3 months, increasing to 1.12 ± 0.49 (p = .003) at 6 months. The urinary NGF/Cr level at baseline demonstrated a low diagnostic accuracy in predicting a better response to the BoNTA treatment (area under the curve = 0.661; p = .047) and no correlation with the urodynamic parameters. The urinary NGF/Cr at baseline or its reduction at the first month following treatment does not serve as a predictor for the response to the BoNTA injections or for urodynamic changes.

Safety and efficacy of trigonal BTX-A injections for children with neurological detrusor overactivity secondary to spinal cord injury

ObjectiveTo evaluate the efficacy and safety of trigonal botulinum toxin A (BTX-A) injections for children with neurological detrusor overactivity (NDO) secondary to spinal cord injury (SCI). MethodsFrom February 2012 to December 2018, children with NDO secondary to SCI were enrolled. All patients received 200U BTX-A intradetrusor injections including the trigone. Videourodynamic study was performed at baseline and 12 weeks after injection. The primary outcome measures were the presence of vesicoureteral reflux and standardized urodynamic measures. Secondary outcomes included incontinence quality of life questionnaire (I-QoL), voiding volume, urinary incontinence episodes, and complete dryness. ResultsA total of 33 pediatric inpatients (28 male and 5 female) completed the study. No one developed VUR at week 0 or week 12. At the first instance of NDO, maximum detrusor pressure (PdetmaxFNDO) and NDO duration were reduced by 29.8% and 31.8%, respectively, whereas NDO volume (VFNDO) increased by 50.5%,12 weeks after injection. Mean urinary incontinence episodes were reduced by 31.7%, whereas voiding volume and I-QOL were increased by 52.9% and 23.3%. 3 patients reported mild transient hematuria during the first week after injection. ConclusionsOur results suggest that the use of bladder-trigone-including intradetrusor BTX-A injection does not induce VUR, and is safe and effective in children with NDO secondary to SCI. Type of studyA prospective self-controlled trial Level of evidenceLevel II

Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée

The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

Long-term discontinuations of botulinum toxin A intradetrusor injections for neurogenic detrusor overactivity: a multicenter study

PurposeData on long-term outcomes of intradetrusor injections of botulinum toxin A (BTX-A) for neurogenic detrusor overactivity (NDO) are lacking. The aim of the present manuscript was to assess the outcomes of intradetrusor injections of BTX-A for NDO after more than 10 years of follow-up. MethodsA retrospective chart review of all consecutive neurological patients who had received either onabotulinumtoxin A or abobotulinumtoxin A intradetrusor injections for NDO between January 2002 and November 2007 at three academic centers, was performed. The primary outcome measure was 10 years discontinuation rate. Other outcomes of interest were: failure, reasons for discontinuation and subsequent treatments of NDO. Discontinuation-free and failure-free survivals were estimated using Kaplan-Meier analyzes. Results140 patients were included in the study. Ten-year discontinuation-free survival and failure-free survival rates were 49.1% and 73% respectively. The most common reason for discontinuation was failure (43.7%; primary and secondary in 17.2% and 26.5% of cases respectively). Secondary failure occurred after a median number of 8 injections and a median time of 80.1 months from the first injection. Other reasons for discontinuation were: patient’s decision (28.1%), non BTX-A related improvement of urinary incontinence (14.1%), progression of the neurological condition (12.5%) and adverse event (1.6%). Discontinuation-free survival was significantly poorer in spina bifida patients compared to patients with multiple sclerosis or spinal cord injury (p= 0.02). ConclusionsOver a half of NDO patients discontinue intradetrusor BTX-A within the first 10 years after the first injection. Spina Bifida patients are at high risk of discontinuation.

Protocol for a prospective observational study of cortical lower urinary tract control changes following intradetrusor injection of botulinum toxin-A in patients with multiple sclerosis

IntroductionMultiple sclerosis (MS) is a severe debilitating disease that affects patients' quality of life. Up to 90% of patients with MS will develop lower urinary tract dysfunction within the first...

Outcomes of intra-detrusor injections of botulinum toxin in patients with spina bifida: A systematic review.

Bladder management in spina bifida patients relies on clean intermittent catheterization and oral antimuscarinics with a significant failure rate. The efficacy of intradetrusor injections of botulinum toxin has been confirmed in patients with spinal cord injury or multiple sclerosis but not in patients with myelomeningocele. To conduct a systematic review of current evidence regarding the efficacy of intra-detrusor injections of Botulinum Toxin A (BTX-A) in spina bifida patients with neurogenic detrusor overactivity (NDO) refractory to antimuscarinics. A research has been conducted on Medline and Embase using the keywords: ("spina bifida" OR "myelomeningocele" OR "dysraphism") AND "toxin." The search strategy and studies selection were performed using the PICOS method according to the PRISMA statement. Twelve published series were included (n = 293 patients). All patients were <18 years old. There was no randomized study comparing BTX-A versus placebo and most studies had no control group. Most studies reported a clinical and urodynamic improvement with resolution of incontinence in 32-100% of patients, a decrease in maximum detrusor pressure from 32 to 54%, an increase of maximum cystometric capacity from 27 to 162%, and an improvement in bladder compliance of 28-176%. Two studies suggested lower efficacy in patients with low compliance bladder compared to those with isolated detrusor overactivity. Intradetrusor injections of BTX-A could be effective in children with spina bifida but this assumption is not supported by high level of evidence studies. There is no data available in adult patients. Neurourol. Urodynam. 36:557-564, 2017. © 2016 Wiley Periodicals, Inc.

AB203. A randomized trial of trigone-including versus trigone-excluding intradetrusor injection of BTX-A for decreasing detrusor leak point pressure in patients with urinary incontinence secondary to spinal cord injury in China

ObjectiveTo compare the safety and efficacy of trigone-including versus trigone-excluding intradetrusor injection of botulinum toxin A (BTX-A) for decreasing detrusor leak point pressure (DLPP) in patients with urinary incontinence (UI) secondary to spinal cord injury (SCI) in China.MethodsA prospective, multicenter, single-blind and randomized controlled trial (RCT) was conducted between December 2012 and June 2015. Patients with UI and low compliance bladder secondary to SCI were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (control group) or 160 U intradetrusor and 40 U intratrigonal injections (experimental group). Patients were evaluated at baseline, and 4, 12 weeks after injection. The efficacy and safety outcomes included DLPP, detrusor leak point volume (LPV), I-QoL, voiding volume, UI episodes, complete dryness. Vesicoureteral reflux (VUR) and other adverse events were recorded.ResultsEighty-six patients were recruited and 80 (41 in experimental group and 39 in the control group) of them completed the trial. There were no significant differences in baseline evaluation items (gender, age, duration of SCI, level of neurological injury, AIS scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group than in the control group for DLPP (−25.66 vs. −19.70 cmH2O, P=0.02), DLPV (116.09 vs. 87.34 mL, P=0.03), I-QoL (27.02 vs. 20.32, P=0.02), mean UI episodes (−7.19/d vs. −6.65/d, P=0.01), complete dryness (22 vs. 10, P=0.01),mean voiding volume (142.84 vs. 110.36 mL, P=0.01). In both of two groups, no patients developed VUR.ConclusionsTrigone-including intradetrusor injection of BTX-A are more effective than those excluding the trigone to decrease DLPP for patients with UI and poor compliant bladders secondary to SCI. It does not induce VUR.

The role of botulinum toxin A in treating neurogenic bladder.

Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox®, Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport®, Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future.

Combined detrusor-trigone BTX-A injections for urinary incontinence secondary to neurogenic detrusor overactivity.

Objectives:The objective of this study was to evaluate the effect and safety of trigonal injection of botulinum toxin A (BTX-A) for patients with neurological detrusor overactivity (NDO) with incontinence.Methods:A prospective, multicenter, single-blind and randomized controlled trial was conducted between June 2011 and June 2014. Spinal cord injury patients with urinary incontinence secondary to NDO overactivity were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (the control group) or 160 U intradetrusor and 40 U intratrigonal injections (the experimental group). Patients were evaluated at baseline and at 4 and 12 weeks after injection. The efficacy and safety outcomes included Incontinence-Specific-Quality-of-Life Instrument (I-QoL), voiding volume, urinary incontinence episodes, complete dryness, maximum detrusor pressure (Pdetmax) and volume at first involuntary detrusor contraction (VFIDC). Vesicoureteral reflux (VUR) and other adverse events were recorded.Results:Ninety-six patients were recruited and 91 of them completed the trial. Among the 91 patients, 47 were randomized to the experimental group and 44 to the control group. There were no significant differences in baseline evaluation items (gender, age, duration of spinal cord injury, level of neurological injury, AIS (the American Social Injury Association) scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group compared with that in the control group for I-QoL (26.01 vs 18.75, P=0.01), mean urinary incontinence episodes (−5.22 vs −4.68 per day, P=0.01), complete dryness (13 vs 5, P=0.03), mean voiding volume (159.72 vs 139.07 ml, P=0.02), Pdetmax (−33.34 vs −28.02 cmH2O, P=0.04) and VFIDC (106.81 vs 97.86 ml, P=0.02), duration of first detrusor contraction (−41.54 vs −18.65 s, P=0.03) and the number of patients with detrusor contraction (−20 vs −9, P=0.02). In both the groups, no patients developed VUR.Conclusions:BTX-A intradetrusor and intratrigonal injections are more effective compared with those excluding the trigone for patients with NDO with incontinence. Intratrigonal injections do not induce VUR.

Effect and safety of trigone-including intradetrusor injection of botulinum toxin A in patients with neurogenic detrusor overactivity and incontinence: a prospective, multicenter, single-blind and randomized controlled trial

Objective To evaluate the effect and safety of trigone-including intradetrusor injection of botulinum toxin A (BTX-A) for patients with neurogenic detrusor overactivity (NDO) and incontinence. Methods A prospective, multicenter, single-blind and randomized controlled trial was conducted between June 2011 and June 2014. Patients with NDO and incontinence who suffered from spinal cord injury were recruited. At a 1∶1 ratio patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (control group) or 160 U intradetrusor plus 40 U intratrigonal injections (experimental group). Patients were evaluated at baseline, 4 and 12 weeks after injection. The primary outcomes included incontinence specific quality of life (I-QOL), mean voiding volume, mean incontinence episodes, complete dryness, maximum detrusor pressure (Pdetmax) during filling, volume at first involuntary detrusor contraction (VFIDC). Vesicoureteral reflux (VUR) and other adverse events were recorded. Results Ninety-six patients were recruited and 91 of them completed the trial. Among the 91 patients, 47 were randomized to experimental group, 44 to control group. There were no significant differences in baseline evaluation items between the 2 groups. All outcomes after treatment improved significantly as compared to the baseline in each group (P<0.05). Twelve weeks after treatment, the improvement percentage of I-QOL (65.84%), mean incontinence episodes (71.95%), complete dryness (29.79%), mean voiding volume (79.47%), Pdetmax (48.76%), VFIDC (64.56%) in experimental group had significant difference as compared to those in control group (55.81%, 65.80%, 11.36%, 69.76%, 40.68%, 57.23%) (P=0.01, 0.02, 0.03, 0.02, 0.04, 0.02), respectively. In both groups, no patients developed VUR. Three cases (1 in experimental group, 2 in control group) developed urinary tract infection. Conclusions Trigone-including intradetrusor injection of BTX-A is more effective than intradetrusor injection excluding the trigone for patients with NDO and incontinence. Intratrigonal injection does not induce VUR. Key words: Urinary bladder, overactive; Urinary bladder, neurogenic; Botulinum toxin type A; Bladder trigone; Treatment outcome

Botulinum Toxin A Intradetrusor Injection for Treating Neurogenic Detrusor Overactivity, A Single Centre Experience.

To evaluate the efficacy and safety of Botulinum Toxin A (BoNTA) intradetrusor injections in patients with neurogenic detrusor overactivity. All patients provided clinical history and voiding diary, submitted to clinical examination, urine culture; serum creatinine; imaging, including plain abdominal X-rays, abdomino-pelvic ultrasonography and voiding cystourethrogram; and urodynamic tests (CMG) . They were managed by intradetrusor injections of BoNTA. For the typical patient, 300 units of BoNTA were injected through 30 injections of 10 u/mL intradetrusally into equally spaced sites of the bladder wall, excluding the trigone, under cystoscopic guidance. Patients were commenced clean intermittent catheterizations (CICs) every 4-6 h post-injection. Follow up included voiding diaries, abdomino-pelvic ultrasonography, serum creatinine and CMG, were completed for all patients at 6 and 12 weeks. This study used IBM SPSS Version 20.0 for statistical analysis. Forty-five patients (28 males and 17 females) with a mean age of 19.6 years were subjected to BoNTA intradetrusor injections. A good clinical response (dry patient either completely or more than 50% of the period between CICs) was observed in 68.9 and 66.7% of the patients after 6 and 12 weeks of follow up, respectively. In the group that responded well, the mean bladder volume increased post-injection by 48.2% and the mean maximum intravesical pressure decreased to 35.3 cm H2 O, a 33.4% improvement. No patients had side-effects related to BoNTA or to the procedure, and no patients experienced a deterioration of their renal functions. Intradetrusor BoNTA injections provide a good clinical response. The urodynamic parameters significantly improved in patients with neurogenic detrusor overactivity.

How to define a refractory idiopathic overactive bladder?

To present the different definitions of "refractory" IOAB. A review of the literature based on PubMed and Cochrane library databases has been conducted. The criteria for defining the success or failure of antimuscarinic treatment and the different definitions of refractory IOAB used in studies evaluating the effects of posterior tibial nerve stimulation, sacral neuromodulation and intradetrusor botulinum toxin-A injections, have been presented. The primary endpoints of these studies were compared. Additionally, different definitions of refractory IOAB were retrieved. There are discrepancies in the definition of "refractory" IOAB in the literature. The definitions of antimuscarinic success in clinical trials are not always transposable into daily practice. Moreover, these clinical trial endpoints do not explore the entirety of a meaningful patient-centered outcome. The failure of antimuscarinic treatments may be defined by different factors, including lack and loss of efficacy, intolerance to side effects, contraindications, willingness of patients to go further with treatment and inadequacy of patient's expectations. Ideally, the best functional outcomes would assess patient's expectations and the physician's objectives and objective measurements. Finally, assessing quality of life might be the most reliable outcome to measure, by considering of all the discussed data. An appropriate definition is complex and needs to consider subjective tools. The "refractory" IOAB needs to be more specifically defined so that alternative treatments can be used at the appropriate time.

Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study

This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence. Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one. Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH₂O during the filling phase decreased from eight to two out of 13 (p = 0.041). Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

RISK OF URINARY TRACT INFECTION AFTER DETRUSOR BOTULINUM TOXIN A INJECTIONS FOR REFRACTORY NEUROGENIC DETRUSOR OVERACTIVITY IN PATIENTS WITH NO ANTIBIOTIC TREATMENT

Study Type – Harm/Safety (case series) Level of Evidence 4 OBJECTIVE To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. PATIENTS AND METHODS This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox® (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport® (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. RESULTS In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. CONCLUSION The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary.

Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment

To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox® (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport® (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary.

Cost Analysis of Interventions for Antimuscarinic Refractory Patients With Overactive Bladder

To estimate average, initial, and cumulative procedure related costs from a US payer perspective extending up to 3 years for the overactive bladder (OAB) interventions: sacral neuromodulation (SNM), intra-detrusor botulinum toxin A (BoNTA), and augmentation cystoplasty (AC) for antimuscarinic refractory patients. Costs (2007 US dollars) were calculated using Current Procedural Terminology (CPT) codes, Ambulatory Payment Classification (APC) codes; Diagnosis Related Group (DRG) payments, and Healthcare Common Procedure Coding System (HCPCS) Level II Codes extracted from the literature and from the SNM device manufacturer. CPT codes were converted to costs using the Center for Medicare and Medicaid Services (CMS) Relative Value Unit (RVU) fee schedule. Sensitivity analyses were performed to evaluate assumptions and uncertainty of results based on plausible variation in estimates of key cost drivers. The initial treatment cost was $22,226, $1,313, and $10,252 for SNM, intra-detrusor injection of BoNTA, and AC respectively. The first-year cost was $23,614, $2626, and $11,637 respectively. Three years after initiating treatment, the cumulative cost was $26,269, $7651, and $14,337 respectively. Sensitivity analyses revealed that SNM persisted as the most costly intervention in all scenarios. The 3-year cumulative cost range produced by the sensitivity analyses for SNM, BoNTA, and AC was $25,384-$27,357, $4586-$11,476, and $12,315-$16,830, respectively. All estimates of cost endpoints for SNM were greater than those for BoNTA and AC. These cost estimates, when combined with data on outcomes and risks, are important components of a robust health care technology assessment of antimuscarinic treatment failure options.