Clinical Efficacy and Changes of Urothelial Dysfunction after Repeated Detrusor Botulinum Toxin A Injections in Chronic Spinal Cord-Injured Bladder Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment. Therapeutic effects of detrusor botulinum toxin A injection on neurogenic detrusor overactivity in patients with different levels of spinal cord injury and types of detrusor sphincter dyssynergia Submucosal Administration of OnabotulinumtoxinA in the Treatment of Neurogenic Detrusor Overactivity: Pilot Single-Centre Experience and Comparison with Standard Injection into the Detrusor An exploratory, placebo-controlled, dose–response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity Repeated botulinum toxin type A injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates. Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence. Intradetrusor versus suburothelial onabotulinumtoxinA injections for neurogenic detrusor overactivity: a pilot study Detrusor botulinum toxin A injection significantly decreased urinary tract infection in patients with traumatic spinal cord injury Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. Efficacy and safety of low doses of onabotulinumtoxinA for the treatment of refractory idiopathic overactive bladder: a multicentre, double-blind, randomised, placebo-controlled dose-ranging study. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. Botulinum toxin type B: An effective treatment for alleviating pain associated with cervical dystonia. OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Activity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial.
Chornic spinal cord injury ( SCI ) will induce bladder urothelium dysfunction . This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA ( BoNT-A ) in SCI patients with neurogenic detrusor overactivity ( NDO ) . Twenty chronic suprasacral SCI patients with NDO were enrolled . The patients received 300 U BoNT-A injection into the detrusor every six months . The urothelium was assessed by cystoscopic biopsy at baseline and six months after each BoNT-A treatment . Immunofluorescence staining for urothelial dysfunction , including E-cadherin , zonula occludens-1 ( ZO-1 ) , tryptase for mast cell activity , and urothelial apoptosis were investigated . The outcome of urothelial dysfunction parameters after BoNT-A injection were compared between baseline and six months after each treatment . Repeated 300 U BoNT-A injections showed a sustained decrease of detrusor pressure compared with baseline . After three repeated BoNT-A detrusor injections , significantly greater distributions of E-cadherin ( p = 0.042 ) and ZO-1 ( p = 0.003 ) expressions , but no significant changes , of urothelial apoptosis and mast cell activation were found after repeated BoNT-A therapy . Urothelial dysfunction , such as adhesive and junction protein concentrations in SCI patients ’ bladders , recovered after three repeated cycles of BoNT-A treatment . The therapeutic effects sustained . However , urothelial inflammation and apoptosis after SCI were not significantly improved after three repeated BoNT-A injections BACKGROUND An increasing body of evidence suggests a possible role of suburothelial myofibroblasts ( MFs ) in bladder mechanosensation and in the pathophysiology of detrusor overactivity ( DO ) . OBJECTIVE To determine whether markers of MFs , including gap junction protein connexin43 ( Cx43 ) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO ( NDO ) or idiopathic DO ( IDO ) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A ( BoNTA ) . DESIGN , SETTING , AND PARTICIPANTS Patients with NDO ( n=10 ) or IDO ( n=11 ) were treated in a single-centre , open-label study of intradetrusor BoNTA injections . Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder ( OAB ) symptoms . This study is registered with Clinical Trials.gov , number NCT00662064 . INTERVENTIONS Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment . They were studied with quantitative immunofluorescence using antibodies to connexin 43 ( Cx43 ) , vimentin , and c-kit . MEASUREMENTS Differences in Cx43 , vimentin , and c-kit immunoreactivity between control subjects and NDO or IDO patients ( primary outcomes ) . Changes in NDO or IDO , Cx43 immunoreactivity , and c-kit immunoreactivity after BoNTA treatment ( secondary outcomes ) . RESULTS AND LIMITATIONS Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls , but remained unchanged after BoNTA treatment . C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment . CONCLUSIONS Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO . It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality . Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs Study design : The study was design ed as a single-arm clinical trial . Objectives : To investigate the therapeutic effects of detrusor botulinum toxin A ( BoNT-A ) treatment in patients with different levels of spinal cord injury ( SCI ) and types of detrusor sphincter dyssynergia ( DSD ) . Setting : Patients with chronic suprasacral SCI and neurogenic detrusor overactivity ( NDO ) were treated with 200-U BoNT-A detrusor injection in a tertiary university hospital in Taiwan . Methods : Outcome assessment of urodynamic parameters and therapeutic satisfaction were performed at 3 and 6 months among patients with different demographics , SCI levels and types of DSD . The treatment outcomes were assessed by changes in Urogenital Distress Inventory 6-item short form ( UDI-6 ) , quality of life ( QoL ) index and detrusor pressure at maximum flow rate ( Pdet . Qmax ) . Results : A total of 38 patients with a mean age of 40.1±12.4 years and median duration of SCI of 10.3 years were enrolled . Satisfactory response was reported in 23 ( 60 % ) patients . Significant improvements in the UDI-6 and QoL were reported and significant increases of cystometric bladder capacity and post-void residual were noted in overall patients after treatment . Patients with different clinical demographics and urodynamic parameters had similar treatment outcomes and UDI-6 scores . In 11 patients receiving repeat injections of 300 U of BoNT-A after failure of a previous 200 U injection , the treatment outcomes were not significantly different , except that the PdetQmax at 6 months were higher in the group that received 200 U of BoNT-A. Conclusion : Patients with different SCI levels or DSD types had similar treatment outcomes after detrusor 200 U BoNT-A injections for NDO Introduction : Apart from the st and ard intramural administration of botulinum neurotoxin A ( BoNT/A ) to the detrusor , intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. Methods : An open , r and omised , prospect i ve study was performed on a total of 23 patients with neurogenic detrusor overactivity . Following r and omisation , patients were treated with 300 U of onabotulinumtoxinA ( onaBoNT/A ) in either the submucosa or the detrusor . Urodynamic examinations were carried out , and a bladder diary was kept both prior to and 12 weeks after the treatment . All patients stopped taking anticholinergics 1 week prior to the treatment . Results : In both the submucosa and detrusor groups , we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment . A comparison of the two groups showed no significant difference between the two forms of application , with the exception of voided volume ( p = 0.007 ) . Conclusion : A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor . Thus , the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients Purpose To explore the dose response to onabotulinumtoxinA 50 , 100 , and 200 U in patients with spinal cord injury ( SCI ) with urinary incontinence ( UI ) due to neurogenic detrusor overactivity ( NDO ) . Methods Patients ( N = 73 ) with SCI ( level T1 or lower ) with NDO and UI ( ≥14 UI episodes/week ) received 30 intradetrusor injections of onabotulinumtoxinA ( 50 U [ n = 19 ] , 100 U [ n = 21 ] , or 200 U [ n = 17 ] ) or placebo ( n = 16 ) via cystoscopy , avoiding the trigone . Changes from baseline in UI episodes/week , volume voided/micturition , maximum cystometric capacity , and maximum detrusor pressure ( MDP ) during first involuntary detrusor contraction ( IDC ) were evaluated . Adverse events ( AEs ) were assessed . Results A significant linear dose response for UI episodes/week was identified at weeks 18 , 30 , 36 , 42 , and 54 ( P < 0.05 ) with a similar trend ( P = 0.092 ) at week 6 ( primary time point ) . A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 ( P < 0.05 ) and in MDP during first IDC at week 6 ( P = 0.034 ) . The proportion of patients who achieved continence at week 6 was highest in the 200 U group . Duration of effect was longest with the 200 U dose , compared with other treatment groups . The AEs were comparable across groups ; urinary tract infection was the most common AE across all treatment groups . Conclusions In this exploratory dose – response study of SCI patients with UI due to NDO , onabotulinumtoxinA 200 U was the most effective dose . The AE profile was comparable across all groups BACKGROUND Efficacy and safety of botulinum toxin type A ( BoNTA ) injection is supported by level 1 evidence , but data regarding repeated injections are limited in patients with refractory overactive bladder ( OAB ) and idiopathic detrusor overactivity ( IDO ) . OBJECTIVES Describe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve data from a single centre were collected from the first 100 patients . INTERVENTION Bladder injection of BoNTA ( predominantly 200 U onabotulinumtoxinA ; Allergan Ltd. , Marlow , Buckinghamshire , UK ) in an outpatient setting . MEASUREMENTS OAB symptoms , quality of life , discontinuation rates , interinjection interval , and adverse events were recorded . Data comparisons were performed using a generalised linear model or a chi-square test where appropriate . RESULTS AND LIMITATIONS Two hundred seven injections were performed in 100 patients . All patients had 1 injection , 53 had a total of 2 , 20 had 3 , 13 had 4 , 10 had 5 , 5 had 6 , 3 had 7 , 1 had 8 , 1 had 9 , and 1 had 10 injections . Statistics were applied up to five repeated injections . A statistically significant reduction in frequency , urgency , and urge urinary incontinence were seen following the first BoNTA injection compared to baseline . This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections . Thirty-seven patients stopped treatment after the first two injections ; thereafter , dropouts were rare . The most common reasons for discontinuing treatment were poor efficacy ( 13 % ) and clean intermittent self-catheterisation (CISC)-related issues ( 11 % ) . The incidence of CISC after the first injection was 35 % . Bacteriuria was detected in 21 % of patients . The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients . CONCLUSIONS BoNTA can provide a safe and effective medium-term management option for patients with refractory IDO . The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues OBJECTIVE To evaluate the impact of botulinum toxin type A ( BoNTA ) on health-related quality of life in patients with neurogenic urinary incontinence ( UI ) using the Incontinence Quality of Life question naire ( I-QOL ) . METHODS R and omized , double-blind , multicenter , placebo-controlled study involving eight centers across Belgium , France , and Switzerl and . Patients ( n = 59 ) with UI due to neurogenic detrusor overactivity ( spinal cord injury , n = 53 ; multiple sclerosis , n = 6 ) who were inadequately managed on oral anticholinergics  received a single dose of BoNTA ( 200U or 300U , Botox ) or placebo .  I-QOL scores at screening and after treatment at weeks 2 , 6 , 12 , 18 , and 24 were recorded . RESULTS Median total and subscale I-QOL scores increased significantly from screening with BoNTA 300U compared with placebo at all time points ( p<0.05 ) and with BoNTA 200U compared with placebo at all time points for total score and the Avoidance Limiting Behavior subscale ( p<0.05 ) , and at weeks 2 , 6 , 12 , and 18 ( p<0.05 ) , but not 24 for the Psychosocial Impact and Social Embarrassment subscales . Approximately twice as many BoNTA recipients as placebo recipients achieved at least a minimal important difference in total I-QOL score at 2 , 6 , 12 , and 24 wk . CONCLUSIONS BoNTA significantly improves UI-associated health-related quality of life in patients with neurogenic UI Study design : This was a multicentre , prospect i ve , r and omised study . Objectives : To compare the outcomes of intradetrusor and suburothelial onabotulinumtoxinA injections in patients with spinal cord injury and refractory neurogenic detrusor overactivity ( NDO ) . Setting : Urology departments of two tertiary hospitals in the Czech Republic . Methods : A total of 32 spinal cord injury patients with severe NDO refractory to the st and ard anticholinergic treatment were r and omised to receive either intradetrusor or suburothelial 300 IU onabotulinumtoxinA injections .  Subjective satisfaction , bladder diary data and urodynamic data were compared in both groups before treatment and at 3 months post treatment . Results : In all , 64.3 % patients in the intradetrusor group and 88.8 % patients in the suburothelial group were subjectively satisfied with the treatment . There was a significant post-treatment improvement in both groups regarding the number of catheterisations over 24 h , number of incontinence episodes over 24 h , catheterised volume , cystometric capacity , volume at first involuntary detrusor contraction , maximal detrusor pressure during filling and detrusor compliance . No significant differences between the groups were observed , with the exception of improvement of detrusor compliance , which was better in the intradetrusor group . There was one adverse effect comprising transient muscle weakness that was reported by one patient in the intradetrusor group . Conclusion : Results in both groups were comparable . The authors favour suburothelial onabotulinumtoxinA injection because this method allows more precise toxin localisation Study design : The study was design ed as a single-arm clinical trial . Objectives : To investigate the effect of detrusor botulinum toxin A ( BoNTA ) injection on urinary tract infection ( UTI ) in patients with spinal cord injury ( SCI ) . Setting : The study was performed in a national rehabilitation research center of China . Methods : Between September 2010 and May 2012 , 41 male in patients with neurogenic detrusor overactivity ( NDO ) caused by traumatic SCI , mean age 36.0±8.8 years , duration of SCI since inclusion 21.5±17.3 months , received an injection of 300 U BoNTA into detrusor . Before and 3 months after injection , each patient kept a bladder diary , underwent video-urodynamic investigation and urine culture . All UTIs occurring in the 6 months before and the 6 months after injection were recorded . Results : Before injection , the mean number of UTI over 6 months was 1.39±1.36 . After injection , the mean significantly decreased to 0.78±0.96 ( P=0.023 ) . The mean maximum detrusor pressure during filling decreased significantly in the patients of detrusor overactivity ( n=24 ) compared with patients of normo-active detrusor ( n=17 ) after injection ( 35.4±12.2 vs 20.9±7.9 cmH2O , P=0.000 ) , meantime , the decrease of UTI was significant in the former ( 1.29±1.21 vs 0.41±0.62 cmH2O , P=0.015 ) while no significant in the latter ( 1.46±1.47 vs 1.04±1.08 , P=0.319 ) . Conclusion : Detrusor BoNTA injection significantly decreased UTI in SCI patients with NDO . This effect seems to be related to the decrease of detrusor pressure AIMS 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 . METHODS Patients with UI due to NDO ( from multiple sclerosis or spinal cord injury ) were r and omized to  intradetrusor placebo ( n = 92 ) or onabotulinumtoxinA 200 U ( n = 92 ) or 300 U ( n = 91 ) . PROs included Incontinence Quality of Life ( I-QOL ) Question naire to assess health-related quality of life ( HRQoL ) , the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Question naire ( OAB-PSTQ ) to assess treatment satisfaction , and Patient Global Assessment to assess treatment goal achievement . RESULTS 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 clinical ly 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 % ) . CONCLUSIONS 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 clinical ly relevant differences between onabotulinumtoxinA doses BACKGROUND In the treatment of patients with idiopathic overactive bladder ( iOAB ) , high doses of botulinum toxin type A ( BoNTA ) were often associated with complications result ing from high postvoid residuals ( PVR ) , leading to clean intermittent catheterisation ( CIC ) and urinary tract infections ( UTI ) . OBJECTIVE Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB . DESIGN , SETTING , AND PARTICIPANTS Between 2005 and 2009 , adults with persistent iOAB were included in a prospect i ve , r and omised , double-blind , placebo-controlled comparative trial . INTERVENTION Patients were r and omised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA ( 50 U , 100 U or 150 U ) . MEASUREMENTS The initial evaluations ( ie , clinical and urodynamic variables as well as quality of life [ QoL ] ) were repeated at day 8 and months 1 , 3 , 5 , and 6 . RESULTS AND LIMITATIONS Ninety-nine patients were included in the efficacy analysis . Three months after the procedure , we observed>50 % improvement versus baseline in urgency and urge urinary incontinence ( UUI ) in 65 % and 56 % of patients who respectively received 100 U ( p=0.086 ) and 150 U ( p=0.261 ) BoNTA injections and > 75 % improvement in 40 % of patients of both groups ( 100 U [ p=0.058 ] and 150 U [ p=0.022 ] ) . Complete continence was observed in 55 % and 50 % patients after 100 U and 150 U BoNTA treatment , respectively , at month 3 . Frequency symptoms and QoL improved up to the 6-mo visit . We observed only three patients with a PVR>200 ml in the 150 U group and a few UTIs . CONCLUSIONS 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB . Nevertheless , 100 U injections showed a reasonable efficacy , with a lower risk of high PVR . TRIAL REGISTRATION Clinical Trials.gov NCT00231491 OBJECTIVE To determine the safety and efficacy of botulinum toxin type B ( BoNT/B ) in patients with cervical dystonia ( CD ) . BACKGROUND BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD . METHODS The authors performed a 16-week , r and omized , multicenter , double-blind , placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo , or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinical ly in CD . The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure . Clinical assessment s and adverse events were recorded for treatment day 1 and at weeks 2 , 4 , 8 , 12 , and 16 . RESULTS A total of 109 patients were enrolled r and omly across all three treatment groups . The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 ( placebo ) , 9.3 ( 5,000 U ) , and 11.7 ( 10,000 U ) . For the prospect ively defined primary contrast ( 10,000 U versus placebo ) , highly significant differences were noted for the primary ( TWSTRS-Total , baseline to week 4 , p = 0.0004 ) and supportive secondary ( Patient Global Assessment , baseline to week 4 , p = 0.0001 ) outcome measures . Improvement in pain , disability , and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients . Overall , improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose . The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses . CONCLUSION Botulinum toxin type B ( NeuroBloc ) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia PURPOSE Several studies have shown that intradetrusor injections of botulinum neurotoxin type A ( BoNT/A ) may effectively treat intractable spinal neurogenic detrusor overactivity ( NDO ) , but fewer reports exist on the use of BoNT/A in patients with idiopathic detrusor overactivity ( IDO ) . The purpose of this study was to investigate whether comparable efficacy could be displayed in the response of patients with IDO to those with NDO . MATERIAL S AND METHODS In a prospect i ve , open label study , patients with urgency , and /or urgency incontinence due to urodynamically proven intractable detrusor overactivity received 300 units ( NDO ) or 200 units ( IDO ) of Botox injected into the bladder with a minimally invasive outpatient technique . Urodynamic maximum cystometric capacity and maximum detrusor pressure during filling , frequency of voids ( frequency ) , number of incontinence episodes ( leak ) and number of voids associated with urgency per 24 hours ( urgency ) from 4-day voiding diaries were compared between the 2 groups at baseline and for changes at 4 and 16 weeks after treatment . RESULTS A total of 44 patients with spinal NDO and 31 with IDO were treated . At 16 weeks , mean + /- st and ard error maximum cystometric capacity increased from 229.1 + /- 24.8 to 427.0 + /- 26.9 ml , p < 0.0001 in NDO and from 193.6 + /- 24.0 to 327.1 + /- 36.1 ml , p=0.0008 in IDO . Maximum detrusor pressure during filling decreased from 60.7 + /- 6.8 to 26.1 + /- 3.7 cm H2O , p < 0.0001 in NDO and from 62.1 + /- 10.8 to 45.1 + /- 8.1 cm H2O , p=0.027 in IDO . Frequency decreased from 12.3 + /- 0.7 to 6.6 + /- 0.6 voids per 24 hours , p < 0.0001 in NDO and from 13.6 + /- 1.1 to 8.3 + /- 0.7 , p=0.0002 in IDO . Leak decreased from 3.9 + /- 0.5 to 0.7 + /- 0.2 incontinence episodes per 24 hours , p < 0.0001 in NDO and from 3.2 + /- 0.8 to 0.6 + /- 0.3 , p=0.0017 in IDO , and urgency decreased from 7.5 + /- 0.6 to 1.44 + /- 0.3 episodes per 24 hours , p < 0.0001 in NDO and from 10.9 + /- 1.7 to 4.9 + /- 1.1 , p < 0.0001 in IDO . The 2 groups were comparable for baseline data , but percent improvement in urgency was greater in patients with NDO at 4 weeks ( 78.2 % vs 56.3 % , p=0.019 ) and 16 weeks ( 78.3 % vs 50.7 % , p=0.013 ) . Of patients with NDO 69 % required self-catheterization de novo posttreatment compared with 19.3 % of those with IDO . CONCLUSIONS Patients with intractable IDO respond to intradetrusor BoNT/A with equally significant improvements in urodynamic and lower urinary tract symptom parameters as those with spinal NDO , despite the lower dose of toxin used Neck pain is reported in 75 % is strongly associated with greater disability and decreased quality of life .  Botulinum toxin type B ( BoNT-B ; Myobloc ) is a new botulinum toxin that has been proven safe and effective in reducing the pain , severity , and disability of patients with cervical dystonia . We analyzed a subset of efficacy data from two r and omized , double blind , placebo-controlled clinical trials . The first study consisted of three treatment groups in patients who were responders to the type A toxin , including placebo  ( n=36 ) , 5000 units ( U ) ( n=36 ) , 10,000 U ( n=37 ) . The second study consisted of placebo ( n=38 ) and 10,000-U treatment groups ( n=39 ) in patients not responding to the type A toxin . For this analysis , the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-subscale scores for pain and three visual analog scales ( Patient Analog Pain , Patient Global , and Principal Investigator Global Assessment s ) were evaluated . A dose-response effect was observed in the reduction of pain based on the TWSTRS-subscale scores . In both studies , mean improvements from baseline to week 4 for all patients were significant compared with placebo ( P<0.005 ) . BoNT-B also significantly improved mean values for all VAS assessment s. Our analysis confirms that BoNT-B significantly reduces the pain associated with  cervical dystonia  and improves patients ' overall condition . This clinical benefit suggests that BoNT-B may be useful in other pain syndromes involving involuntary muscle spasms or contractions Introduction To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity ( NDO ) in sub population s of etiology ( multiple sclerosis [ MS ] or spinal cord injury [ SCI ] ) and concomitant anticholinergics ( use/non-use ) . Methods Data were pooled from two double-blind , placebo-controlled , pivotal , phase 3 studies including a total of 691 patients with ≥14 urinary incontinence ( UI ) episodes/week due to MS ( n = 381 ) or SCI ( n = 310 ) . Patients received intradetrusor injections of onabotulinumtoxinA 200U ( n = 227 ) , 300U ( n = 223 ) , or placebo ( n = 241 ) . Change from baseline at week 6 in UI episodes/week ( primary endpoint ) , urodynamics , quality of life ( QOL ) , and adverse events ( AEs ) were assessed . Results Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use : at week 6 , mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients , respectively , and −20.3 and −22.5 in anticholinergic users and non-users , respectively , treated with onabotulinumtoxinA 200U . The 300U dose did not add to the clinical efficacy in any sub population . Similar proportions of patients achieved ≥50 % or 100 % reductions in UI episodes in all subgroups . Improvements in maximum cystometric capacity , maximum detrusor pressure during first involuntary detrusor contraction , and QOL were significant in both etiologies and were independent of anticholinergic use . The most common AEs in all groups were urinary tract infection and urinary retention . Conclusion Regardless of concomitant anticholinergic use or etiology , onabotulinumtoxinA significantly improved UI symptoms , urodynamics , and QOL  in patients with UI due to NDO . OnabotulinumtoxinA was well tolerated in all groups PURPOSE We assessed the efficacy , safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity . MATERIAL S AND METHODS In this 52-week , international , multicenter , double-blind , r and omized , placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence ( 14 or more episodes per week ) result ing from multiple sclerosis ( 227 ) and spinal cord injury ( 189 ) were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo . The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6 . Maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points . Adverse events were monitored . RESULTS OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week , respectively , vs 9 episodes per week in 149 on placebo ( each dose p<0.001 ) . Also , maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group ( each dose p<0.001 ) . Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo ( 256 and 254 days , respectively , vs 92 ) . The most common adverse events were urinary tract infection and urinary retention . Of patients who did not catheterize at baseline 10 % on placebo , 35 % on 200 U and 42 % on 300 U initiated catheterization due to urinary retention . CONCLUSIONS OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo . Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion . No clinical ly relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose BACKGROUND Neurogenic detrusor overactivity ( NDO ) frequently results in urinary incontinence ( UI ) which impairs quality of life ( QOL ) and puts the upper urinary tract at risk . OBJECTIVE To assess the effects of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) on UI , urodynamic variables , and QOL in incontinent patients with NDO . DESIGN , SETTING , AND PARTICIPANTS This multicentre , r and omised , double-blind , placebo-controlled study enrolled patients with multiple sclerosis ( MS ; n=154 ) or spinal cord injury ( SCI ; n=121 ) with UI due to NDO ( ≥14 UI episodes per week ) . INTERVENTION Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U ( n=92 ) , 300 U ( n=91 ) , or placebo ( n=92 ) , avoiding the trigone . MEASUREMENTS Primary end point was change from baseline in UI episodes per week ( week 6 ) . Secondary end points included urodynamics ( maximum cystometric capacity [ MCC ] , maximum detrusor pressure during first involuntary detrusor contraction [ P(detmaxIDC ) ] ) , and Incontinence Quality of Life ( I-QOL ) total score . Adverse events ( AEs ) were assessed . RESULTS AND LIMITATIONS At baseline , mean UI episodes per week ( 33.5 ) were similar across groups . At week 6 , onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week ( -21.8 and -19.4 , respectively ) compared with placebo ( -13.2 ; p<0.01 ) ; onabotulinumtoxinA benefit was observed by the first posttreatment study visit at week 2 . Improvements in MCC , P(detmaxIDC ) , and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo ( p<0.001 ) . Benefits were observed in both the MS and SCI population s. The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses ( 42.1 wk ) and greater than placebo ( 13.1 wk ; p<0.001 ) . Most frequent AEs were localised urologic events ( urinary tract infections and urinary retention , which were dose related in patients not using clean intermittent catheterisation [ CIC ] at baseline ) . Significant increases in postvoid residual were observed in patients not using CIC prior to treatment , and 12 % , 30 % , and 42 % of patients in the placebo , 200-U , and 300-U groups , respectively , initiated CIC posttreatment . CONCLUSIONS OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO . Both doses were well tolerated with no clinical ly relevant differences in efficacy or duration of effect between the two doses ( http://www . clinical trials.gov ; NCT00461292 )
There were no statistically significant differences between doses of 200 U and 300 U or between injections into the detrusor and submucosa .
CONCLUSION BoNT-A is effective and safe in treating NDO after SCI .
There were no statistically significant differences between doses of 200 U and 300 U or between injecting into the detrusor and submucosa .
PURPOSE OnabotulinumtoxinA ( BoNT-A ) is a promising therapy for treating neurogenic detrusor overactivity ( NDO ) in individuals with spinal cord injury ( SCI ) .
This systematic review and meta- analysis aim ed to carry out an in-depth review and to make an objective estimation of the efficacy and safety of BoNT-A on NDO after SCI .