Clinical Efficacy and Changes of Urothelial Dysfunction after Repeated Detrusor Botulinum Toxin A Injections in Chronic Spinal Cord-Injured Bladder 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 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 The possible role of percutaneous tibial nerve stimulation using adhesive skin surface electrodes in patients with neurogenic detrusor overactivity secondary to spinal cord injury OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Activity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. Detrusor botulinum toxin A injection significantly decreased urinary tract infection in patients with traumatic spinal cord injury Intradetrusor versus suburothelial onabotulinumtoxinA injections for neurogenic detrusor overactivity: a pilot study Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. The therapeutic effects of repeated detrusor injections between 200 or 300 units of onabotulinumtoxinA in chronic spinal cord injured patients. Submucosal Administration of OnabotulinumtoxinA in the Treatment of Neurogenic Detrusor Overactivity: Pilot Single-Centre Experience and Comparison with Standard Injection into the Detrusor OnabotulinumtoxinA improves quality of life in patients with neurogenic detrusor overactivity Efficacy and tolerability of propiverine hydrochloride extended-release compared with immediate-release in patients with neurogenic detrusor overactivity Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan‐neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment Efficacy of botulinum toxin A injection for neurogenic detrusor overactivity and urinary incontinence: a randomized, double-blind trial. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. Neuropathic pain post spinal cord injury part 1: systematic review of physical and behavioral treatment. Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment.
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 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 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 Purpose To compare the effectiveness of percutaneous tibial nerve stimulation ( PTNS ) using adhesive skin surface electrodes versus solifenacin succinate ( SS ) in patients with neurogenic detrusor overactivity ( NDO ) secondary to spinal cord injury ( SCI ) . Methods A r and omized controlled study involving 100 patients with NDO secondary to SCI was conducted . Patients were r and omized into two groups . In group A , patients received PTNS using adhesive skin surface electrodes for 4 weeks . In group B , patients underwent SS treatment for 4 weeks . Bladder diaries and incontinence quality of life question naire were review ed before treatment and 2 and 4 weeks after treatment . Results Improvement in all bladder diary parameters was statistically significant within each group 2 and 4 weeks after treatment compared to baseline ( p < 0.05 ) , but did not reach statistical significance between the PTNS and SS groups ( p > 0.05 ) . Compared to SS , PTNS was not associated with any unanticipated adverse events . Conclusions PTNS therapy with adhesive skin surface electrodes is an effective method to treat NDO secondary to SCI . This therapy is not only no difference comparing to SS therapy but also noninvasive and easily managed by patients 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 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 ) 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 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 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 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 OBJECTIVES To investigate the therapeutic effects of repeated detrusor onabotulinumtoxinA injections on treatment outcomes , quality of life ( QoL ) , and glomerular filtration rate ( GFR ) in chronic spinal cord injured ( SCI ) patients with neurogenic lower urinary tract dysfunction and urinary incontinence . MATERIAL S AND METHODS Patients with SCI who failed antimuscarinic treatment were enrolled . All patients had urodynamic detrusor overactivity ( DO ) or increased detrusor tonicity without anatomical bladder outlet obstruction or intrinsic sphincter deficiency . They were r and omly assigned to receive 200-U or 300-U onabotulinumtoxinA detrusor injections every 6 months . The primary endpoint was 6 months after the second injection . The urodynamic parameters , QoL measures , and 99mTc renal scans were evaluated at baseline and every 3 months and compared between dosages . RESULTS A total of 72 patients were enrolled , including 43 men and 29 women and mean injury duration of 8.7 years . Among them , 38 patients received 200-U and 34 received 300-U onabotulinumtoxinA injections . At the end-point , the urodynamic parameters and incontinence severity improved significantly , without a significant difference between the two groups . QoL also improved in both groups , without differences between groups . Uninhibited DO improved more in 300-U group compared to 200-U group at end-point ( P = 0.01 ) . The GFR did not change significantly in either group . The most common complication was urinary tract infection , which occurred in one third of patients . CONCLUSIONS Either 200-U or 300-U repeated detrusor onabotulinumtoxinA injections improved incontinence , urodynamic parameters , and QoL in SCI patients with neurogenic DO . Renal function was maintained in patients receiving both dosage of repeated injections 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 Objective : To evaluate the effects of onabotulinumtoxinA on patient-reported outcomes including health-related quality of life ( HRQOL ) , treatment satisfaction , and treatment goal attainment in patients with urinary incontinence ( UI ) due to neurogenic detrusor overactivity ( NDO ) . Methods : In this multicenter , double-blind , r and omized , placebo-controlled , phase III , 52-week study ( Clinical Trials.gov NCT00311376 ) , patients with UI due to NDO who were not adequately managed with anticholinergic therapy were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo ( 0.9 % saline ) . HRQOL measures included the Incontinence Quality of Life ( I-QOL ) Question naire total score , and the 3 domain scores ( avoidance and limiting behavior , psychosocial , and social embarrassment ) , the modified Overactive Bladder Patient Satisfaction with Treatment Question naire ( OAB-PSTQ ) , and Patient Global Assessment . Assessment s were made at baseline , posttreatment week 6 ( primary time point ) , week 12 , and at 12-week intervals . Results : Patients ( mean age of 46 years with 30.5 weekly UI episodes at baseline ) were r and omized to receive placebo ( n = 149 ) or onabotulinumtoxinA ( 200 U [ n = 135 ] or 300 U [ n = 132 ] ) . At week 6 , improvements from baseline in I-QOL Question naire total score were greater ( p < 0.001 ) in both onabotulinumtoxinA-treated groups vs placebo . Responses to the OAB-PSTQ also demonstrated greater mean improvements from baseline ( p < 0.001 ) in both onabotulinumtoxinA-treated groups vs placebo at week 6 . Patients who received onabotulinumtoxinA also reported greater improvement in the Patient Global Assessment than those in the placebo group ( p ≤ 0.001 vs placebo ) . Conclusions : Patients with UI due to NDO reported greater improvement in HRQOL and treatment satisfaction with onabotulinumtoxinA than with placebo consistently across several patient-reported outcome instruments . Classification of evidence : This study provides Class I evidence that onabotulinumtoxinA intradetrusor injections ( 200 or 300 U ) can improve quality of life measures in patients with NDO not adequately managed with anticholinergic therapy Study design : Double-blind , r and omised , multicentre study . Objectives : Efficacy and tolerability of propiverine extended-release ( ER ) compared with immediate-release ( IR ) were evaluated in patients with proven neurogenic detrusor overactivity ( NDO ) . Setting : Six Spinal Cord Injury Units located in Austria , Germany and Romania . Methods : Propiverine ER 45 mg s.i.d . or IR 15 mg t.i.d . were administered in patients with proven NDO . Outcomes were assessed at baseline ( V1 ) , and after 21 days of treatment ( V2 ) : Reflex volume served as primary , leak point volume and maximum detrusor pressure as secondary efficacy outcomes , treatment-related adverse events as tolerability outcomes . Results : Sixty-six patients with proven NDO were enrolled .  Reflex volume ( ml ) increased significantly in the IR ( V1 : 100.9 , V2 : 202.9 ) and in the ER ( V1 : 89.8 , V2 : 180.3 ) group , no significant intergroup difference . Leak point volume increased , and maximum detrusor pressure decreased significantly in both groups , no significant intergroup differences . The percentage of patients presenting with incontinence was reduced by 14 % in the IR and by 39 % in the ER group , the difference is significant . Treatment-related adverse events manifested in 42 and 36 % following propiverine IR and ER , respectively . Conclusion : The urodynamic efficacy outcomes demonstrated both galenic formulations to be equieffective . However , following propiverine ER 45 mg s.i.d . higher continence rates compared with propiverine IR 15 mg t.i.d . were achieved , possibly indicative of more balanced plasma-levels . A slight tendency for superior tolerability outcomes of propiverine ER compared with IR was demonstrated . Sponsorship : The study was sponsored by an unrestricted educational grant of APOGEPHA Arzneimittel GmbH , Dresden , Germany Background The control of the lower urinary tract is a complex , multilevel process involving both the peripheral and central nervous system . Due to lesions of the neuraxis , most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction , which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life . However , the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood . Methods / Design This is a prospect i ve structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity . Neuroimaging data will include structural magnetic resonance imaging ( T1-weighted imaging and diffusion tensor imaging ) as well as functional , i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner . The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system . All subjects will undergo two consecutive and identical magnetic resonance imaging measurements . Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity . Parameters of the clinical assessment including bladder diary , urinalysis , medical history , neuro-urological examination , urodynamic investigation as well as st and ardised question naires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis . Discussion This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls . Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control . Trial registration Clinical Trials.gov NCT01768910 To compare PGP9.5 and transient receptor potential vanilloid receptor ( TRPV1 ) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity ( NDO ) before and after treatment with intravesical resiniferatoxin , as suburothelial PGP9.5‐staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin , and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder PURPOSE We determined the efficacy of onabotulinumtoxinA for neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis . MATERIAL S AND METHODS In a prospect i ve , double-blind , multicenter study 57 patients 18 to 75 years old with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis and urinary incontinence ( defined as 1 or more occurrences daily ) despite current antimuscarinic treatment were r and omized to  onabotulinumtoxinA 300 U ( 28 ) or placebo ( 29 ) via cystoscopic injection at 30 intradetrusor sites , sparing the trigone . Patients were offered open label onabotulinumtoxinA 300 U at week 36 and followed a further 6 months while 24 each in the treatment and placebo groups received open label therapy . The primary efficacy parameter was daily urinary incontinence frequency on 3-day voiding diary at week 6 . Secondary parameters were changes in the International Consultation on Incontinence Question naire and the urinary incontinence quality of life scale at week 6 . Diary and quality of life evaluations were also done after open label treatment . RESULTS The mean daily frequency of urinary incontinence episodes was significantly lower for onabotulinumtoxinA than for placebo at week 6 ( 1.31 vs 4.76 , p < 0.0001 ) , and for weeks 24 and 36 . Improved urodynamic and quality of life parameters for treatment vs placebo were evident at week 6 and persisted to weeks 24 to 36 . The most common adverse event in each group was urinary tract infection . CONCLUSIONS In adults with antimuscarinic refractory neurogenic detrusor overactivity and multiple sclerosis onabotulinumtoxinA is well tolerated and provides clinical ly beneficial improvement for up to 9 months 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 Neuropathic pain has various physiologic and psychosocial aspects . Hence , there is a growing use of adjunct nonpharmacological therapy with traditional pharmacotherapy to reduce neuropathic pain post spinal cord injury ( SCI ) . OBJECTIVE The purpose of this study was to conduct a systematic review of published research on nonpharmacological treatment of neuropathic pain after SCI . METHODS MEDLINE , CINAHL , EMBASE , and PsycINFO data bases were search ed for articles addressing nonpharmacological treatment of pain post SCI . Articles were restricted to the English language . Article selection was conducted by 2 independent review ers with the following inclusion criteria : the subjects participated in a treatment or intervention for neuropathic pain ; at least 50 % of the subjects had an SCI ; at least 3 subjects had an SCI ; and a definable intervention was being studied . Data extracted included study design , study type , subject demographics , inclusion and exclusion criteria , sample size , outcome measures , and study results . R and omized controlled trials ( RCTs ) were assessed for quality using the Physiotherapy Evidence Data base ( PEDro ) assessment scale . Levels of evidence were assigned to each intervention using a modified Sackett scale . RESULTS The 16 articles selected for this review fell into 1 of 2 categories of nonpharmacological management of pain after SCI : physical and behavioral treatments . The pooled sample size of all studies included 433 participants . Of the 16 studies included , 7 were level 1 , 3 were level 2 , and 6 were level 4 studies . CONCLUSIONS Physical interventions demonstrated the strongest evidence based on quality of studies and numbers of RCTs in the nonpharmacological treatment of post-SCI pain . Of these interventions , transcranial electrical stimulation had the strongest evidence of reducing pain . Despite a growing body of literature , there is still a significant lack of research on the use of nonpharmacological therapies for SCI pain 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
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 .