How to define failure of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) has a major impact on patients' quality of life and can lead to upper urinary tract complications. Intradetrusor botulinum toxin type A injections are administered as second-line treatment to these patients following the failure of anticholinergic agents. The aim of the DETOX 2 study is to propose a consensus definition of the failure of intradetrusor botulinum toxin injections for NDO in patients presenting spinal cord injury, spina bifida, or multiple sclerosis (MS) with self-catheterization. METHOD: This study followed the method adopted by the French National Authority for Health for recommendations by consensus. Based on a review of the literature and a preliminary survey, a steering committee compiled a questionnaire and selected a rating group comprising 16 experts from the Neuro-Urology Committee of the French Urology Association (cnuAFU) and Genulf. The experts were asked to complete the online questionnaire. At the end of the first round, all participants came together to discuss any disagreements and a second-round online questionnaire was completed to reach a consensus. RESULTS: Thirteen of the 16 experts approached completed both rounds of questionnaires. A strong consensus was reached for two proposals (median score = 9/10) which were therefore included in the definition from the first round: at least one repeat injection of the same botulinum toxin at the same dose must be given to rule out failure on technical grounds and a duration of efficacy <3 months must be considered a failure. At the end of round 2, a relative consensus was reached regarding the clinical criterion defining failure (median score = 7/10) and the urodynamic criterion of failure (median score = 8/10). An additional proposal was selected during this second round on the need for a voiding diary (median score = 8/10). CONCLUSION: The first consensus definition of failure of an intradetrusor injection of TB-A for NDO has been achieved with this study: persistence of detrusor overactivity with maximum detrusor pressures >40 cm H2O and/or a compliance issue and/or persistence of urinary incontinence and/or urgency and/or a number of daily self-catheterizations >8/day and/or efficacy <3 months. This study will help to standardize research on the failure of the intradetrusor botulinum toxin for NDO in clinical practice and clinical research.

Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation-A study from the neuro-urology committee of the French Association of Urology.

BACKGROUND: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). OBJECTIVES: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. METHODS: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. RESULTS: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing-remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. CONCLUSION: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.

Efficacy and safety of intradetrusor botulinum toxin injections for idiopathic overactive bladder syndrome in patients with an artificial urinary sphincter.

PURPOSE: To assess the efficacy and safety of intradetrusor botulinum toxin type A injections (IBTI) for idiopathic overactive bladder (iOAB) in non-neurological adults with an artificial urinary sphincter (AUS). MATERIALS AND METHODS: We retrospectively selected, in the 11 French centers, members of a collaborative network (GENULF (Groupe d'étude de neuro-urologie de langue francaise)), the patients who had had an artificial urinary sphincter implantation and who had subsequently developed iOAB requiring IBTI. This study was approved by the French association of urology ethics committee (no 2018012). RESULTS: Between 2006 and 2020, 33 patients were included from 5 French centers. Mean follow-up after the first IBTI was 47 months. The average age of the studied population was 68 years, with 70% of females. A complete resolution of symptoms at optimal IBTI dose was experienced by 21 (64%) patients. Seven (21%) patients had partial improvement. Five non-responder patients (15%) had no improvement at all. Maximum cystometric bladder capacity was 240 ml pre-IBTI and 335 ml post IBTI. Discontinuation free survival at 60 months was 50%. Two erosions occurred during the 6 months following an IBTI both in male patients with a perineal implantation. There were four AUS balloon perforations that occurred during the 6 months following an IBTI, all of them in female patients. CONCLUSIONS: IBTI has a good efficacy for the treatment of iOAB in patients with an AUS. However, both patients and practicians must be aware of the risk of rare and usually mild complications.

Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial.

BACKGROUND: Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. METHODS: Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. RESULTS: Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5-2.5) in the WOCA group versus 2.5 (1.2-4.0) (P = .0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P < .001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0-2.0) versus 3.0 (2.0-5.0) (P = .004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. CONCLUSIONS: WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. CLINICAL TRIALS REGISTRATION: NCT01388413.

Management of urethrocutaneous fistulae complicating sacral and perineal pressure ulcer in neurourological patients: A national multicenter study from the French-speaking Neuro-urology Study Group and the Neuro-urology committee of the French Association of Urology.

PURPOSE: To describe the epidemiologic characteristics of urethrocutaneous fistulae (UCF) in sacro-perineal pressure ulcer (SPPU) in neurourological patients and to assess outcomes after surgical urinary diversion. MATERIALS AND METHODS: Through the French-speaking Neurourology Study Group and Association of Urology network, a retrospective multicenter study in nine major urology and physical medicine and rehabilitation (PMR) units was conducted. All patients with SPPU associated with UCF between 2000 and 2016 were included. Data concerning: sociodemography, clinical, medical and biological comorbidities, neurological and urological history, pressure ulcer characteristics, and finally urinary diversion surgery were collected. Complications and SPPU healing/relapse were assessed. RESULTS: In all, 74 patients were included. The median age on diagnosis: 45.9 years (interquartile range [IQR], 38.7-53.4) and median follow-up: 15.1 months (IQR, 5.7-48.8). A psychiatric disorder was the most frequent comorbidity (44.6%). Only 59.5% and 50% had regular PMR and urologic follow-up, respectively. Seventy-one patients (95.9%) underwent urinary diversion surgery. Among those, relapse occurred in 15 (21.1%) at the end of the follow-up. The diversion was noncontinent in 85.9%. The major complications rate was 26.8%. A total of 30 late complications in 21 patients were reported. The most frequent was obstructive pyelonephritis (n = 9). All of the patients who underwent surgical diversion without cystectomy (n = 5) developed a pyocyst. Finally, the pressure ulcer healing rate when patients underwent both urinary diversion and pressure ulcer surgery was 74.4%. CONCLUSIONS: Our retrospective data suggest that UCF complicating SPPU is a rare and severe pathology. The combination of radical urinary diversion with cystectomy and pressure ulcer surgery should be performed as often as possible.

Botulinum Toxin Type A Injection After Failure of Augmentation Enterocystoplasty Performed for Neurogenic Detrusor Overactivity: Preliminary Results of a Salvage Strategy. The ENTEROTOX Study.

OBJECTIVE: To evaluate the clinical efficacy, urodynamic effect and safety of Botulinum Toxin A (BTXA) injections after failure of augmentation enterocystoplasty (AE) performed for neurogenic detrusor overactivity. PATIENTS AND METHODS: We performed a multicenter retrospective study that included patients who had AE and at least one injection of BTXA after AE in 15 GENULF (French Speaking Neuro-Urology Study Group) centers. Clinical and urodynamic data were collected from medical files according to a standardized questionnaire and colligated in an anonymous database. RESULTS: Thirty-three patients with an injection of BTXA after AC in 9 out of 15 centers were included. Mean age at the time of AE was 24 ± 15 years. Overall efficacy (defined by clinical efficacy associated with a request by the patient for reinjection) was observed in 58% of the patients. Mean maximum cystomanometric capacity increased by 28% (333 ± 145 vs 426 ± 131 mL; P = .007) and maximum detrusor pressure (Pdet max) decreased by 43% (44 ± 37 vs 25 ± 18 cm H2O; P = .02) after BTXA. Only one side effect was recorded out of the 152 procedures (transient generalized muscle weakness without respiratory distress). CONCLUSION: In patients with failure after AE performed for neurogenic detrusor overactivity, injection of BTXA in the enlarged bladder was effective in over half of the cases with low morbidity. If this therapeutic approach were confirmed, it could be proposed as an alternative to AE surgical revision.

Urological dysfunction in patients with hereditary spastic paraplegia.

AIMS: Purposes of this study were to describe lower urinary tract symptoms (LUTS) and related urodynamic patterns in patients with hereditary spastic paraplegia (HSP), and to characterize LUTS management and associated uronephrological complications. METHODS: We retrospectively reviewed medical files of HSP patients, consecutively followed in our Physical and Rehabilitation Medicine Department between 1999 and 2016. Clinical, urodynamic, and radiological data were collected and analyzed. Different treatments which have been prescribed and uronephrological complications were also recorded. Patients with other neurological or urological diseases were excluded. RESULTS: Thirty-three patients with HSP were included. Mean duration of follow-up was 8.1 ± 5 years, mean age 62 ± 14 years, and 70% were men. The most frequent LUTS was urgency and voiding dysfunction (both 69.7%). Incontinence and retention with a significant postvoid residue above 100 mL accounted for 66.7% and 57.6% of initial symptoms respectively. Neurogenic detrusor overactivity was diagnosed in 80.7% of patients. Two-thirds of our cohort were treated with anticholinergics and 9.1% required intradetrusor botulinum-toxin injections. Only 27.3% of patients performed clean intermittent self-catheterization. Febrile urinary tract infections (21.2%), urolithiasis (15,1%), hydronephrosis (6%), and chronic renal failure (9.1%) were found. CONCLUSION: Given their high prevalence and the risk of uronephrological complications, LUTS should be systematically assessed in HSP patients. The systematic screening of urological dysfunction in this population would improve its management, decrease the incidence of uronephrological complications, and increase the quality of life.

Intradetrusor Injections of Botulinum Toxin A in Adults with Spinal Dysraphism.

PURPOSE: The aim of the current study was to determine the outcomes of botulinum toxin A intradetrusor injections in adult patients with spina bifida. MATERIALS AND METHODS: All patients with spinal dysraphism who underwent intradetrusor injections of botulinum toxin A from 2002 to 2016 at a total of 14 centers were retrospectively included in analysis. The primary end point was the global success of injections, defined subjectively as the combination of urgency, urinary incontinence and detrusor overactivity/low bladder compliance resolution. Univariate and multivariate analysis was performed to seek predictors of global success. RESULTS: A total of 125 patients were included in study. The global success rate of the first injection was 62.3% with resolution of urinary incontinence in 73.5% of patients. All urodynamic parameters had improved significantly by 6 to 8 weeks compared to baseline, including maximum detrusor pressure (-12 cm H2O, p <0.001), maximum cystometric capacity (86.6 ml, p <0.001) and compliance (8.9 ml/cm H2O, p = 0.002). A total of 20 complications (3.6%) were recorded for the 561 intradetrusor botulinum toxin A injections, including 3 muscular weakness complications. The global success rate of the first injection was significantly lower in patients with poor compliance (34.4% vs 86.9%, OR 0.08, p <0.001). On multivariate analysis poor compliance was associated with a lower global success rate (OR 0.13, p <0.001). Female gender (OR 3.53, p = 0.01) and patient age (OR 39.9, p <0.001) were predictors of global success. CONCLUSIONS: Intradetrusor botulinum toxin A injections were effective in adult patients with spina bifida who had detrusor overactivity. In contrast, effectiveness was much lower in adult patients with spina bifida who had poor bladder compliance. The other predictors of global success were female gender and older age.

Long-term outcomes and risks factors for failure of intradetrusor onabotulinumtoxin A injections for the treatment of refractory neurogenic detrusor overactivity.

AIMS: Aims of this study were to assess the long-term outcomes of Intradetrusor injection of OnabotulinumtoxinA (Botox® injection) associated with clean intermittent-catheterization (CIC) for the treatment of neurogenic detrusor overactivity (NDO) and to identify risk factors for failure. METHODS: Neurological patients with NDO using CIC who had received Botox® injections between January 2001 and September 2013 were included. Clinical, urodynamic and radiological data were recorded. Primary endpoint was failure and withdrawal rates after 3, 5, and 7 years of management. Survival curves of withdrawals and failures of treatment were calculated with a 95-confidence interval using the Kaplan-Meier method. Risk factors for failure were determined with univariate analysis and multivariate analysis using Cox model. RESULTS: Overall, 292 patients, mean age of 40 ± 13, 6 years, were included. Overall, 219 patients (80.6%; IC95% [76.3-85.4%]) were still treated with Botox® injections after 3 years, 128 (71.1%; IC95% [65.7%, 76.9%]) after 5 years, and 58 (60.8%, IC95% [54.0%, 68.4%]) after 7 years. Failure rate was 12.6% (IC95% [8.6-16.5%]) after 3 years, 22.2% (IC95% [16.6-27.3%]) after 5 years, and 28.9% (IC95% [21.9%; 35.3%]) after 7 years of follow-up. Withdrawal rate after 7 years of follow-up was 11.3% (n = 33/292). Severe NDO at baseline appears to be a significant risk factor for failure. CONCLUSION: This study confirms long-term efficacy and tolerance of Botox® injection in patients with NDO using CIC. Long-term failure and withdrawal rates remain low but significant, and need to be managed.

Sacral neuromodulation and pregnancy: Results of a national survey carried out for the neuro-urology committee of the French Association of Urology (AFU).

AIMS: To assess the impact of sacral neuromodulation (SNM) on pregnancy and vice-versa, by identifying women who had received SNM for lower-urinary tract symptoms (LUTS) and had become pregnant. METHODS: A cross-sectional descriptive study was carried out based on responses to an on-line questionnaire sent to practitioners listed on the InterStim enCaptureTM National Registry. Questions were related to pre-pregnancy health and SNM efficacy, deactivation of the device, its impact on LUTS, childbirth, the infant, its reactivation and postpartum effectiveness. RESULTS: Twenty-seven pregnancies were recorded among 21 women. Six women had had a pregnancy prior to implantation, two of whom had had a c-section. A total of 18.5% of women had the device disabled prior to conception. The others had their device disabled during the first trimester and did not reactivate it before delivery. Complications were reported in 25.9% of pregnancies: six women had urinary infections, including three of the four treated for chronic retention of urine (CRU), and 1 woman had pain at the stimulation site. There were 24 live births (including one premature birth and four c-sections), one spontaneous miscarriage and two voluntary interruptions of pregnancy. No neonatal disorders have been reported. Effectiveness of sacral neuromodulation decreased in 20% in postpartum. CONCLUSIONS: In 27 pregnancies established during SNM for LUTS, 18.5% of patients deactivated their case before pregnancy and the others switched it off during the first trimester. Three-quarters of women with CRU had urinary infection. No adverse effects on fetuses were found. SNM effectiveness deteriorated in 20% cases after childbirth.

Intradetrusor injection of botulinum toxin A and sacral neuromodulation for neurogenic detrusor overactivity.

Intradetrusor injection of botulinum toxin A and sacral neuromodulation are the two recommended third line treatments for patients with neurogenic detrusor overactivity, before undergoing with surgery. However, only Botox® injection is supported by a high level of evidence allowing its recommendation by all institutional guidelines. Despite few positive results, sacral neuromodulation should be proposed in carefully selected patients. Indeed, other studies remain mandatory to increase its level of evidence necessary for allowing its use in neurogenic detrusor overactivity.

Long-term complications of continent cutaneous urinary diversion in adult spinal cord injured patients.

OBJECTIVE: To report the long-term complications of continent cutaneous urinary diversion(CCUD) in spinal cord injured(SCI) patients unable to perform intermittent self-catheterization(ISC) through the urethra. MATERIALS AND METHODS: Between July 2001 and January 2012, adult SCI patients with a neurogenic bladder who underwent CCUD according to Mitrofanoff's/Monti's/Casale's principle were enrolled. A concomitant supratrigonal and augmentation enterocystoplasty were performed because of refractory detrusor overactivity or low bladder compliance. Early postoperative complications were reported according to Clavien-Dindo classification. Long-term complications, stomal and urethral continence, renal function, urodynamic parameters and quality-of-life were assessed. RESULTS: Overall, 29 consecutive SCI patients were included, median age 35 years (IQR 26-46). Median follow-up time was 66 months (IQR 50-80). Two post-operative severe complications (grade III-IV) were reported. One patient had a stomal stenosis and another patient a tube stenosis. Both were treated by dilation. Two patients developed fistulae between the tube and the skin and required a surgical treatment. Three patients had bladder stones managed with endoscopy. Two patients had remnant stress urine leakage through the urethra, which was treated surgically: one received periurethral balloons(ACTTM ) and one a tension-free vaginal tape. Creatinine clearance remained stable postoperatively. Urodynamic parameters were significantly improved. At last follow-up, 100% of patients had a catheterizable continent stoma and urethral continence was achieved in 96%. An improvement of quality-of-life was reported by 90% of patients. CONCLUSIONS: CCUD allowed these patients to keep ISC as a voiding pattern and to be continent without any appliance. The main complications were related to the tube and to bladder enlargement; thus, annual monitoring is required. Neurourol. Urodynam. 35:1046-1050, 2016. © 2015 Wiley Periodicals, Inc.