Neurogenic Detrusor Overactivity In Patients Research Articles

OnabotulinumtoxinA (Botox A) for Neurogenic Detrusor; Evidence for 200 U vs. 300 U

OnabotulinumtoxinA (Botox A) has gone from investigational to a recognized standard for neurogenic detrusor overactivity (NDO) in patients intolerant or inadequately managed by anticholinergics. A large number of initial studies were done using the 300 unit dose, including the initial report on 200 vs. 300 U. There was a suggestion that 300 units may have some advantage but statistical sample size was small. Two pivotal phase 3 studies compare 200 units to 300 units of BotoxA for NDO. The result of these studies did not show an advantage to the higher dose. These studies did lead to the Food and Drug Administration (FDA) approval, in August 2011, of BotoxA 200 units for refractory or inadequately treated NDO patients. A subsequent pooled extension study was performed. Patients were then followed for five to eight treatment cycles of onabotulinumtoxinA. The data demonstrated no significant increased efficacy of the higher dose of onabotulinumtoxinA for patient management.

Urologic applications of botulinum toxin.

The neuromuscular blocker botulinum toxin has a wide variety of medical applications, including overactive bladder and neurogenic detrusor overactivity in patients in whom drug therapy fails or is not well tolerated. Botulinum toxin therapy for these conditions has been shown to be safe and effective in several large multicenter randomized controlled trials. Off-label uses in urology include detrusor external sphincter dyssynergia and pelvic pain syndromes.

PD1-04 DETRUSOR INJECTIONS OF ONABOTULINUM TOXIN A (BOTOX®) VERSUS ABOBOTULINUM TOXIN A (DYSPORT®) IN THE MANAGEMENT OF NEUROGENIC DETRUSOR OVERACTIVITY : A CASE CONTROL STUDY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction I1 Apr 2015PD1-04 DETRUSOR INJECTIONS OF ONABOTULINUM TOXIN A (BOTOX®) VERSUS ABOBOTULINUM TOXIN A (DYSPORT®) IN THE MANAGEMENT OF NEUROGENIC DETRUSOR OVERACTIVITY : A CASE CONTROL STUDY Benoit Peyronnet, Castel-Lacanal Evelyne, Roumiguie Mathieu, Marque Philippe, Rischmann Pascal, and Game Xavier Benoit PeyronnetBenoit Peyronnet More articles by this author , Castel-Lacanal EvelyneCastel-Lacanal Evelyne More articles by this author , Roumiguie MathieuRoumiguie Mathieu More articles by this author , Marque PhilippeMarque Philippe More articles by this author , Rischmann PascalRischmann Pascal More articles by this author , and Game XavierGame Xavier More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.199AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Onabotulinumtoxin-A (BOTOX®) is the only botulinum toxin whose use is based on multicenter randomized controlled trials and is therefore the only one to be licensed in the US and Europe for the management of neurogenic detrusor overactivity (NDO). However, the use of abobotulinum-toxin A (Dysport®) for NDO is also supported by high level of evidence studies. Only one small sample case-control study has aimed to compare the results of this two toxins in the management of NDO. Our aim was to compare the outcomes of detrusor injections of onabotulinum toxin A and abobotulinum toxin A in NDO patients. METHODS Data of all consecutive patients who underwent a first detrusor injection of botulinum toxin A for NDO at a single-institution between 2006 and 2014 were prospectively collected. In our department, abobotulinum toxin was the only first-line botulinum toxin used to treat NDO from 2006 to 2011 (first era). From 2011, as onabotulinum-toxin A became licensed in US and Europe, we decided to use it as the first-line botulinum toxin (second era: 2011–2014). Detrusor injections were performed at a dose of 200 U for onabotulinum toxin A and at a dose of 750 U for abobotulinum toxin A. Before and 6 weeks after injection, patients carried out a 3-day bladder diary and had urodynamics. The success was defined as the combination of a cllean intermittent self-catheterisation number under 8 per 24 hours, urgency, urinary incontinence and detrusor overactivity relief. Perioperative parameters were compared between the onabotulinum and abobotulinum toxin A groups. RESULTS Two-hundred and eleven patients were included for analysis with respectively 78 in the abobotulinum group (group A) and 133 in the onabotulinum group (group O). Neurological conditions were similar between both groups (multiple sclerosis : 29% vs. 32% ; spinal cord injury : 38% vs. 40% ; others : 33% vs. 28% ; p=0.38). Complete success (based on urodynamic and clinical parameters) was obtained in 66% of patients in group O and in 58% of patients in group A (p=0.27). Relief of urinary incontinence was also achievd similarly in both groups (79% vs. 75%; p=0.45). The relative risk of complete success was 0.9 for group O versus group A (IC 95% : 0.7-1.1). Complication rates were very low and similar in both groups (4% vs. 7% ; p=0.37). CONCLUSIONS Detrusor injections of either onabotulinum toxin A or abobotulinum toxin a provides comparable results in the management of NDO. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e36 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benoit Peyronnet More articles by this author Castel-Lacanal Evelyne More articles by this author Roumiguie Mathieu More articles by this author Marque Philippe More articles by this author Rischmann Pascal More articles by this author Game Xavier More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Short-Term Effect of Percutaneous Bipolar Continuous Radiofrequency on Sacral Nerves in Patients Treated for Neurogenic Detrusor Overactivity After Spinal Cord Injury: A Randomized Controlled Feasibility Study.

ObjectiveTo investigate the short-term effects of bipolar radiofrequency applied to sacral nerves to treat neurogenic detrusor overactivity in patients with spinal cord injury.MethodsTen patients with spinal cord injury with neurogenic detrusor overactivity were recruited. These subjects were randomized to two groups: intervention (n=5) and control (n=5), members of which received conventional treatment. Voiding diary, International Consultation on Incontinence Questionnaire (ICIQ) and the urinary incontinence quality of life scale (IQOL) data were obtained and an urodynamic study (UDS) was performed before and after intervention. In the intervention group, percutaneous bipolar continuous radiofrequency (CRF) was performed on both the S2 and S3 nerves in each patient.ResultsIn a comparison of daily frequency and number of urinary incontinence and ICIQ and IQOL scores at baseline and at 1 and 3 months after intervention, all variables achieved a significant effect for time (p<0.05). Regarding UDS parameters, pre/post intervention differences between baseline and 3-month post-intervention for volume at maximal detrusor pressure during filling and reflex detrusor volume at first contraction were significantly different between the two groups (p<0.05). However, pre/post intervention differences in maximum cystometric capacity and maximum detrusor pressure during filling were not significant between the two groups (p>0.05).ConclusionPercutaneous bipolar CRF applied to sacral nerves might be an effective therapy for neurogenic overactive bladder that reduces urinary incontinence and improves quality of life.

Chapter 4: Guidelines for the diagnosis and treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO).

This chapter focuses on the position of botulinum toxin type A in the treatment pathway for overactive bladder (OAB) and neurogenic lower urinary tract dysfunction associated with neurogenic detrusor overactivity (NDO), and the recommendations of the major international guideline groups. Recommendations of different guideline groups may vary, especially when evidence is weak, often because of differences in methodology and panel composition. Relevant guidelines from the European Association of Urology, American Urological Association, and the UK National Institute for Care and Clinical Excellence were reviewed, and the recommendations that form the basis of the treatment algorithms have been discussed. Any differences between guidelines have been highlighted and special emphasis made on the position of botulinum toxin type A in these pathways. In all the reviewed guidelines, botulinum toxin type A is recommended, alongside sacral nerve neuromodulation, to treat OAB and NDO in patients who have failed oral therapy. The evidence base is consistent, but further evidence is required regarding optimal dosing regimens and injection technique.

Chapter 1: The conditions of neurogenic detrusor overactivity and overactive bladder.

Overactive bladder (OAB) is a symptom syndrome consisting of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence (UUI), in the absence of a causative infection or pathological conditions. The prevalence of OAB is approximately 11-19% in both men and women, and leads to a significant negative effect on a patient's health-related quality of life (HRQOL). OAB is also associated with comorbidities such as urinary tract infection (UTI) and an increased risk of falls. Following behavioral therapy, anticholinergic agents are commonly prescribed, but these often fail because of lack of efficacy and/or poor tolerability. Evaluation of treatment success in OAB should include pre-defined, patient-centered goals. Patients for whom oral therapy has failed to meet such goals may be considered refractory to oral therapy and candidates for minimally invasive therapy. Neurogenic detrusor overactivity (NDO) is a bladder dysfunction frequently observed in patients with conditions such as multiple sclerosis (MS) and spinal cord injury (SCI). Increased storage pressure can put the upper urinary tract at risk of deterioration and reducing this risk is a primary aim of therapy. Urinary incontinence (UI) is reported by approximately 50% of MS patients, and most SCI patients will develop some bladder dysfunction. NDO leads to a negative impact on HRQOL, independent of the impact of the primary condition. NDO patients in whom oral therapy has failed to normalize storage pressure may be considered refractory and are candidates for minimally invasive therapy.

OnabotulinumtoxinA and multiple sclerosis

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended.

Impact of urinary incontinence on health-related quality of life, daily activities, and healthcare resource utilization in patients with neurogenic detrusor overactivity

BackgroundNeurogenic detrusor overactivity (NDO) leads to impaired health-related quality of life (HRQoL), productivity, and greater healthcare resource burden. The humanistic and economic burden may be more apparent in NDO patients with urinary incontinence (UI). The objective of this study was to compare the HRQoL, productivity, and health resource use (HRU) between continent and incontinent NDO patients.MethodsA retrospective database analysis was conducted using the Adelphi Overactive Bladder (OAB)/UI Disease Specific Programme, a multi-national, cross-sectional survey reported from both patients’ and physicians’ perspectives. The population for this analysis included NDO patients with or without UI. General and disease-specific HRQoL were assessed using the EuroQoL-5D (EQ-5D), Incontinence Quality of Life questionnaire (I-QOL), and the Overactive Bladder Questionnaire (OAB-q). Productivity and daily activity impairment were measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. HRU indicators included OAB-related surgery, OAB-related hospitalizations, incontinence pad usage, switching anticholinergics used for OAB due to inadequate response or adverse effects, and OAB-related physician visits. Bivariate analyses, multivariate ordinary least squares (OLS) regression analyses and published minimal clinically important differences (MCID) were used to assess relationships between incontinent status and the aforementioned outcome measures.ResultsA total of 324 NDO patients with or without urinary incontinence were included, averaging 54 years of age (SD 16), of whom 43.8 percent were male. Bivariate analyses detected no significant relationship between incontinent status and HRU variables. Regression analyses revealed that incontinent patients had clinically and statistically lower disease-specific HRQoL and greater impairment in daily activities as compared to continent patients. On average, incontinent patients scored 10 points lower on the I-QOL total score, 9 points lower on the OAB-q HRQoL score, 15 points higher on OAB-q symptom severity, and experienced 8.2 percent higher activity impairment due to their bladder condition (all p < 0.001).ConclusionsIncontinent NDO patients experience significantly lower HRQoL and activity impairment as compared to continent NDO patients.

γEpithelial Na+ Channel and the Acid-Sensing Ion Channel 1 expression in the urothelium of patients with neurogenic detrusor overactivity

Both Epithelial Na+ Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) belong to Degenerin/Epithelial Na+ channel family that represents a new class of cation channels [1]. Increasing evidences show an involvement of these channels in the control of bladder afferent excitability under physiological and pathological conditions [2]; however, data available on their expression in human urothelium are controversial. Pathogenesis of the neurogenic detrusor overactivity (NDO), one of the most severe disabilities reported in patients with spinal cord lesions (SCL), has been attributed to bladder afferent dysfunction. Therefor, the aim of the present study was to investigate the expression of γENaC and ASIC1 in control urothelium and NDO patients. Controls and SCL patients with a clinical diagnosis of NDO underwent to urodynamic measurements and cystoscopy. Cold cup biopsies were processed for immunohistochemistry and western blots. In controls, γENaC and ASIC1 were expressed in the urothelium with different cell distribution and intensity. In NDO patients, both markers showed consistent changes in their cell distribution and intensity. Moreover, a significant correlation between the higher intensity of γENaC expression in urothelium of NDO patients and lower values of bladder compliance was found. In conclusion, the present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Of note, while the changes in γENaC might impair the mechanosensory function of urothelium, the increase of the ASIC1 might represent an attempt to compensate excess in local sensitivity.

Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels

Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson’s disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO), which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM) large conductance Ca2+-activated K+ (BK) channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR), perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs) in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

PND29 - Estimating the cost-effectiveness of onabotulinumtoxinA for neurogenic detrusor overactivity in the United States

Abstract Background Urinary incontinence (UI) secondary to a neurogenic pathology, including spinal cord injury and multiple sclerosis, is termed neurogenic detrusor overactivity (NDO). Patients with NDO experience decreased quality of life and are at risk for upper urinary tract damage. Two recent trials demonstrated that onabotulinumtoxinA significantly reduced UI, improved urodynamic parameters, and improved quality of life relative to placebo. However, the economic impact of onabotulinumtoxinA treatment for UI due to NDO in the United States remains unknown. Objective The objective of this analysis was to evaluate whether the benefit observed in NDO patients receiving onabotulinumtoxinA provides good value for money. Methods We developed a Markov state transition model to estimate population outcomes and costs for anticholinergic-refractory NDO patients who received either onabotulinumtoxinA or best supportive care (use of incontinence pads with either an anticholinergic drug, clean intermittent self-catheterization, or both). Nonresponding patients ( Results In the base case, onabotulinumtoxinA increased QALYs by 0.059 and costs by $1466 compared with best supportive care, which resulted in an estimated ICER of $24,720/QALY. OnabotulinumtoxinA also decreased mean UI episodes per person-year by 398, resulting in a cost of $4 per UI episode avoided. Model results were most sensitive to the probability of treatment response. The probabilistic sensitivity analysis indicated that at a willingness to pay of $50,000/QALY, onabotulinumtoxinA has a 97% probability of being cost-effective. In subgroup analyses of each etiology, onabotulinumtoxinA yielded an ICER of $32,268/QALY in multiple sclerosis and $2182 in spinal cord injury. Conclusion OnabotulinumtoxinA seems to be a cost-effective intervention for UI due to NDO compared with best supportive care.

Estimating the Cost-Effectiveness of OnabotulinumtoxinA for Neurogenic Detrusor Overactivity in the United States

BackgroundUrinary incontinence (UI) secondary to a neurogenic pathology, including spinal cord injury and multiple sclerosis, is termed neurogenic detrusor overactivity (NDO). Patients with NDO experience decreased quality of life and are at risk for upper urinary tract damage. Two recent trials demonstrated that onabotulinumtoxinA significantly reduced UI, improved urodynamic parameters, and improved quality of life relative to placebo. However, the economic impact of onabotulinumtoxinA treatment for UI due to NDO in the United States remains unknown. ObjectiveThe objective of this analysis was to evaluate whether the benefit observed in NDO patients receiving onabotulinumtoxinA provides good value for money. MethodsWe developed a Markov state transition model to estimate population outcomes and costs for anticholinergic-refractory NDO patients who received either onabotulinumtoxinA or best supportive care (use of incontinence pads with either an anticholinergic drug, clean intermittent self-catheterization, or both). Nonresponding patients (<50% reduction in UI episodes at 6 weeks) were eligible to receive invasive procedures, including augmentation cystoplasty or sacral neuromodulation. Patients could transition through 6 health states, 3 defined based on response to initial treatment, 2 capturing patients who underwent invasive procedures, and death. Time in each health state was adjusted for patient quality of life and summed to estimate quality-adjusted life-years (QALYs). The model included direct medical costs related to initial and subsequent drug and invasive treatments, physician visits, and catheterization. Outcomes and costs were summed and compared across intervention groups by using the incremental cost-effectiveness ratio (ICER; cost per QALY). The time horizon of the model was 3 years, and results were discounted at 3%. Scenario, 1-way, and probabilistic sensitivity analyses were performed to test the robustness of the model results. ResultsIn the base case, onabotulinumtoxinA increased QALYs by 0.059 and costs by $1466 compared with best supportive care, which resulted in an estimated ICER of $24,720/QALY. OnabotulinumtoxinA also decreased mean UI episodes per person-year by 398, resulting in a cost of $4 per UI episode avoided. Model results were most sensitive to the probability of treatment response. The probabilistic sensitivity analysis indicated that at a willingness to pay of $50,000/QALY, onabotulinumtoxinA has a 97% probability of being cost-effective. In subgroup analyses of each etiology, onabotulinumtoxinA yielded an ICER of $32,268/QALY in multiple sclerosis and $2182 in spinal cord injury. ConclusionOnabotulinumtoxinA seems to be a cost-effective intervention for UI due to NDO compared with best supportive care.

OnabotulinumtoxinA improves urodynamic outcomes in patients with neurogenic detrusor overactivity

To evaluate the effect of onabotulinumtoxinA on urodynamic outcomes in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO). Results from two pivotal Phase III trials (n = 691) were pooled. MS or SCI patients with NDO, received intradetrusor onabotulinumtoxinA 200 U (n = 227), 300 U (n = 223), or placebo (n = 241). Change from baseline in UI episodes/week (Week 6), maximum cystometric capacity (MCC), maximum detrusor pressure at first involuntary detrusor contraction (IDC) (PdetmaxIDC), volume at first IDC (VpmaxIDC), and detrusor compliance (DC) were measured. OnabotulinumtoxinA significantly increased MCC overall (+153.6 ml with 200 U vs. +11.9 ml with placebo). Over 60% of onabotulinumtoxinA-treated patients had no IDC at Week 6; in patients with an IDC at Week 6, VpmaxIDC improved (+183.4 ml with 200 U vs. +17.5 ml with placebo), and PdetmaxIDC decreased (-32.4 cmH2O with 200 U vs. +1.1 cmH2O with placebo). OnabotulinumtoxinA-treated patients had a significant increase in DC (+59.8 ml/cmH2O with 200 U vs. -5.2 with placebo). Urodynamic improvements were comparable in patients regardless of baseline DC and corresponded with significant reductions in UI episodes/week for both onabotulinumtoxinA doses versus placebo, with no clinically relevant differences between 200 and 300 U groups. Most common adverse event was urinary tract infection (UTI); complicated UTIs were low across all treatment groups. In patients not catheterizing at baseline, a dose-dependent increase in post-void residual urine was observed at Week 2 following onabotulinumtoxinA treatment. OnabotulinumtoxinA significantly improved urodynamic outcomes in NDO patients, even in those with low baseline DC, and corresponded with improvements in UI episodes. Both doses of onabotulinumtoxinA were well tolerated.

Treatment satisfaction and improvement in health‐related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity

OnabotulinumtoxinA significantly reduces urinary incontinence (UI) and improves bladder management in patients with neurogenic detrusor overactivity (NDO). We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes (PROs) in patients with UI due to NDO in a double-blind, placebo-controlled study. Patients with UI due to NDO (from multiple sclerosis or spinal cord injury) were randomized to intradetrusor placebo (n = 92) or onabotulinumtoxinA 200 U (n = 92) or 300 U (n = 91). PROs included Incontinence Quality of Life (I-QOL) Questionnaire to assess health-related quality of life (HRQoL), the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ) to assess treatment satisfaction, and Patient Global Assessment to assess treatment goal achievement. Mean improvement in I-QOL total score at weeks 6 and 12 was significantly greater with both onabotulinumtoxinA 200 U and 300 U versus placebo (Δ12.3 for 200 U and Δ14.9 for 300 U vs. placebo; P < 0.001), and was clinically meaningful. For those patients who completed the OAB-PSTQ, improvement in satisfaction at weeks 6 and 12 was significantly greater for onabotulinumtoxinA versus placebo (P < 0.001, all comparisons). At 6 weeks, greater proportions of onabotulinumtoxinA-treated patients than placebo reported being somewhat or very satisfied (200 U, 77.5% and 300 U, 67.8% vs. placebo, 39.5%), and significant progress toward or complete achievement of primary treatment goal (200 U, 62.9% and 300 U, 61.6% vs. placebo, 16.5%). NDO patients treated with onabotulinumtoxinA 200 or 300 U had significantly greater improvement in HRQoL and greater treatment satisfaction compared with placebo-treated patients, with no clinically relevant differences between onabotulinumtoxinA doses.

1179 CLINICAL EFFICACY OF A NEW BOTULINUM TOXIN TYPE A FREE OF COMPLEXING PROTEINS IN THE TREATMENT OF REFRACTORY NEUROGENIC AND IDIOPATHIC DETRUSOR OVERACTIVITY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy II1 Apr 20121179 CLINICAL EFFICACY OF A NEW BOTULINUM TOXIN TYPE A FREE OF COMPLEXING PROTEINS IN THE TREATMENT OF REFRACTORY NEUROGENIC AND IDIOPATHIC DETRUSOR OVERACTIVITY Teruhiko Yokoyama, Shin Ohira, Masaichiro Fujita, Kazuhiko Fukumoto, Tomohiro Fujii, Yoshimasa Jo, Yoshiyuki Miyaji, Atsushi Nagai, and Keiji Oguma Teruhiko YokoyamaTeruhiko Yokoyama Kurashiki, Japan More articles by this author , Shin OhiraShin Ohira Kurashiki, Japan More articles by this author , Masaichiro FujitaMasaichiro Fujita Kurashiki, Japan More articles by this author , Kazuhiko FukumotoKazuhiko Fukumoto Kurashiki, Japan More articles by this author , Tomohiro FujiiTomohiro Fujii Kurashiki, Japan More articles by this author , Yoshimasa JoYoshimasa Jo Kurashiki, Japan More articles by this author , Yoshiyuki MiyajiYoshiyuki Miyaji Kurashiki, Japan More articles by this author , Atsushi NagaiAtsushi Nagai Kurashiki, Japan More articles by this author , and Keiji OgumaKeiji Oguma Okayama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1424AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In this study, we investigated the efficacy of a new developed neurotoxin type A (NTX) free of complexing proteins for treatment of idiopathic (IDO) and neurogenic detrusor overactivity (NDO) refractory to anti-muscarinic drugs. METHODS This study was approved by the institutional review board. Patients with urgency incontinence due to urodynamically proven detrusor overactivity received 200 units (NDO) or 100 units (IDO for women), or 50 units (IDO for men) of NTX injected into the bladder wall with a minimally invasive outpatient technique by flexible cystoscopy. Maximum cystometric capacity and maximum detrusor pressure were evaluated before and 1 month after treatment by filling cystometry. Subjective and objective measures included frequency of voids and number of incontinence episodes per 24 hours from 3-day bladder diary after 1, 3 months subsequently. RESULTS A total of 16 patients with spinal NDO median age of 34 years (range 20 to 75, 2 females and 14 males) and 33 with IDO median age of 68 years (range 50 to 83, 15 females and 18 males) were treated. The mean maximal cystometric capacity increased from 138±48.2 ml at baseline to 359±130 ml at 1 month (p=0.0033) in NDO, 166±62.0 ml to 288±108 ml (p=0.0009) in IDO. The mean maximal detrusor pressure decreased from 65.9±34.9 cmH2O to 27.3±12.8 cmH2O (p=0.0033) in NDO, 63.5±28.8 cmH2O to 32.3±21.9 cmH2O (p=0.0001) in IDO. The mean number of episodes of urinary incontinence daily decreased from 4.7±2.8 to 1.1±1.6 (p=0.0022) at 1 month, to 2.1±1.6 (p=0.0074) at 3 months inNDO, from 4.5±2.8 to 1.5±2.3 (p=0.0001) at 1 month, to 1.8±1.8 (p=0.0002) at 3 months in IDO. Ten of 16 NDO patients obtained completely continence within 1 month post injection. Thirteen patients (81%) in NDO noted more than half reduction of urinary incontinence episodes after treatment. Fifteen of 33 IDO patients obtained completely continence within 1 month post injection. Twenty three patients (70%) in IDO noted more than half reduction of urinary incontinence episodes after treatment. However, 10 of 33 (30%) patents could not get subjective improvement. Fourteen patients (42%) out of 33 IDO had residual urine volume>100ml at 1 month post treatment and 4 male patients required clean intermittent catheterization for a few weeks. No serious side effects occurred. CONCLUSIONS This newly developed NTX improved bladder capacity and decreased urinary leakage episodes in patients with IDO and NDO. These results suggest that NTX is a promising therapeutic option for these conditions. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e478 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Teruhiko Yokoyama Kurashiki, Japan More articles by this author Shin Ohira Kurashiki, Japan More articles by this author Masaichiro Fujita Kurashiki, Japan More articles by this author Kazuhiko Fukumoto Kurashiki, Japan More articles by this author Tomohiro Fujii Kurashiki, Japan More articles by this author Yoshimasa Jo Kurashiki, Japan More articles by this author Yoshiyuki Miyaji Kurashiki, Japan More articles by this author Atsushi Nagai Kurashiki, Japan More articles by this author Keiji Oguma Okayama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Urothelial TRPV1: TRPV1-Reporter Mice, a Way to Clarify the Debate?

Urothelial TRPV1: TRPV1-Reporter Mice, a Way to Clarify the Debate?

Neurogenic Detrusor Overactivity in Patients With Spinal Cord Injury: Evaluation and Management

Lower urinary tract dysfunction can have a significant impact on patients with spinal cord injury. Over the years, many treatment options have become available. This article reviews the assessment and management of neurogenic detrusor overactivity, with a particular focus on articles from the recent literature. Recent guidelines on the subject will be discussed. Management options include antimuscarinics and bladder emptying measures, botulinum toxin A, and neuromodulation in refractory cases and surgery for intractable cases. Recent and relevant publications in these areas will be summarized and discussed.

Urinary tract dysfunction in Parkinson’s disease: a review

Parkinson's disease is an extrapyramidal neurological disorder. Although motor symptoms are a predominant feature of the condition, non-motor symptoms have also been recognized. Urinary symptoms are frequently present in patients affected with Parkinson's disease (PD). Symptoms such as urgency, frequency, nocturia and urge incontinence significantly impact the patient's quality of life. We discuss the urinary dysfunction seen in patients with Parkinson's disease and consider the pathophysiology, important differentials, the investigations and management options for such patients. An extensive search was performed using the PubMed(®)/EMBASE(®) databases to identify the available literature on urinary disturbances and Parkinson's disease. Reference was also made to current national guidelines on Parkinson's disease. Urinary disturbances are frequently observed in sufferers of Parkinson's disease resulting in significant impact to the individual's quality of life. Studies report that storage symptoms are present in 57-83% of patients, whereas voiding symptoms are seen in 17-27% patients. Out of all the urinary symptoms, nocturia is the most common complaint in >60% patients with PD. Urgency occurs in 33-54% of patients, whilst frequency is experienced by 16-36% of patients. Detrusor overactivity (DO) is the commonest cystometric abnormality in patients with PD. The rate of neurogenic DO in patients with PD is 45-93%. The main differential to consider is Multiple System Atrophy (MSA) in which all patients are ultimately afflicted with urinary disturbance. It is well recognized that patients initially diagnosed with PD may in fact have MSA, and it is important to distinguish the two as their urological management is different. Patients presenting with refractory LUTS with concurrent PD should undergo full urodynamic investigation including cystometry, flowmetry and ultrasonography before treatment is initiated. Referral to a urologist is advised in those with persistent or refractory urinary complaints. Urodynamic evaluation allows determination of the underlying bladder disorder; however, post-void residuals suffice in the uncomplicated patient. The pathophysiology of urinary dysfunction and current investigation and treatment modalities are discussed.

1961 9 YEAR SINGLE CENTRE EXPERIENCE WITH OFF-LABEL BOTULINUMTOXIN A DETRUSOR INJECTIONS IN PATIENTS WITH IDIOPATHIC DETRUSOR OVERACTIVITY (IDO) OR NEUROGENIC DETRUSOR OVERACTIVITY (NDO) REFRACTORY FOR STANDARD TREATMENT – IS TACHYPHYLAXIA A PROBLEM?

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-Neurogenic Voiding Dysfunction1 Apr 20111961 9 YEAR SINGLE CENTRE EXPERIENCE WITH OFF-LABEL BOTULINUMTOXIN A DETRUSOR INJECTIONS IN PATIENTS WITH IDIOPATHIC DETRUSOR OVERACTIVITY (IDO) OR NEUROGENIC DETRUSOR OVERACTIVITY (NDO) REFRACTORY FOR STANDARD TREATMENT – IS TACHYPHYLAXIA A PROBLEM? Christian Hampel, David D′Andrea, Joachim W. Thüroff, and Rolf Gillitzer Christian HampelChristian Hampel Mainz, Germany More articles by this author , David D′AndreaDavid D′Andrea Mainz, Germany More articles by this author , Joachim W. ThüroffJoachim W. Thüroff Mainz, Germany More articles by this author , and Rolf GillitzerRolf Gillitzer Mainz, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2165AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Botulinumtoxin A has proven efficacy in patients with IDO and NDO refractory for antimuscarinics. However, it is not approved in any urological indication. We present our 9 year single-centre experience with off-label detrusor injections for IDO and NDO with a special focus on tachyphylaxia following repeated injections. METHODS Starting in 07/2001, 92 patients with cystometrically confirmed idiopathic detrusor overactivity (IDO) and 78 patients with neurogenic detrusor overactivity (NDO) refractory for standard treatment were injected with 300 U Botulinumtoxin A into the detrusor (10 U per 1 ml injection). Mean patient age was 57 years (12-82). Patients were asked to fill out voiding diaries every month and were allowed to readmit themselves for a booster injection in case of deteriorating results and disease recurrence. RESULTS The intervals between injections do not differ during the first 6 injections. Afterwards, the reinjection intervals tend to shorten (Tab. 1), taking into account the small number of patients with more than 6 injections. CONCLUSIONS Although the data basis is small, tachyphylaxia may play a role in IDO or NDO patients receiving repeated Botulinumtoxin A detrusor injections. Reinjection intervals seem to shorten after 6 injections. The necessary number of reinjections can be estimated according to the patient′s life expectancy and may serve as a guide for treatment stratification (e.g. neuromodulation for younger IDO/NDO patients, Botulinumtoxin A for older patients). © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e785 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian Hampel Mainz, Germany More articles by this author David D′Andrea Mainz, Germany More articles by this author Joachim W. Thüroff Mainz, Germany More articles by this author Rolf Gillitzer Mainz, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-Term Effect on Quality of Life of Repeat Detrusor Injections of Botulinum Neurotoxin-A for Detrusor Overactivity in Patients With Multiple Sclerosis

We studied the effect of repeat detrusor botulinum neurotoxin type A injections on urinary symptoms, health and quality of life in patients with refractory neurogenic detrusor overactivity secondary to multiple sclerosis. This was a prospective, open label, single center study in 137 patients with multiple sclerosis treated with detrusor injections of botulinum neurotoxin type A with observations made from 2002 to 2009. A minimally invasive outpatient technique was used for injection. Patients were asked to contact the department if and when they required repeat treatment. Recurrent detrusor overactivity was then identified on urodynamics. The primary outcomes measured were the change in symptoms and quality of life, as assessed by the Urogenital Distress Inventory, Incontinence Impact Questionnaire and EuroQol-5 Dimensions questionnaires (www.ion.ucl.ac.uk/departments/repair/themes/uroneurology) before and 4 weeks after botulinum treatment. Continence status, the need for clean intermittent self-catheterization before and after injections, and interinjection intervals were also analyzed. Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire 7 scores showed considerable improvement 4 weeks after each treatment even when repeated 6 times. Almost all patients relied on clean intermittent self-catheterization after treatment. Before the first treatment 83% of patients were incontinent but 4 weeks after the first treatment 76% (104 of 137) became completely dry. This efficacy was sustained with repeat injections. The median interval between re-treatments remained constant at 12 to 13 months. Repeated detrusor botulinum neurotoxin type A injections for refractory neurogenic detrusor overactivity in patients with multiple sclerosis have a consistent effect on bladder control, resulting in sustained improvement in quality of life.