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.

Kinematic parameters obtained with the ArmeoSpring for upper-limb assessment after stroke: a reliability and learning effect study for guiding parameter use.

BACKGROUND: After stroke, kinematic measures obtained with non-robotic and robotic devices are highly recommended to precisely quantify the sensorimotor impairments of the upper-extremity and select the most relevant therapeutic strategies. Although the ArmeoSpring exoskeleton has demonstrated its effectiveness in stroke motor rehabilitation, its interest as an assessment tool has not been sufficiently documented. The aim of this study was to investigate the psychometric properties of selected kinematic parameters obtained with the ArmeoSpring in post-stroke patients. METHODS: This study involved 30 post-stroke patients (mean age = 54.5 ± 16.4 years; time post-stroke = 14.7 ± 26.7 weeks; Upper-Extremity Fugl-Meyer Score (UE-FMS) = 40.7 ± 14.5/66) who participated in 3 assessment sessions, each consisting of 10 repetitions of the 'horizontal catch' exercise. Five kinematic parameters (task and movement time, hand path ratio, peak velocity, number of peak velocity) and a global Score were computed from raw ArmeoSpring' data. Learning effect and retention were analyzed using a 2-way repeated-measures ANOVA, and reliability was investigated using the intra-class correlation coefficient (ICC) and minimal detectable change (MDC). RESULTS: We observed significant inter- and intra-session learning effects for most parameters except peak velocity. The measures performed in sessions 2 and 3 were significantly different from those of session 1. No additional significant difference was observed after the first 6 trials of each session and successful retention was also highlighted for all the parameters. Relative reliability was moderate to excellent for all the parameters, and MDC values expressed in percentage ranged from 42.6 to 102.8%. CONCLUSIONS: After a familiarization session, the ArmeoSpring can be used to reliably and sensitively assess motor impairment and intervention effects on motor learning processes after a stroke. Trial registration The study was approved by the local hospital ethics committee in September 2016 and was registered under number 05-0916.

Long-Term Discontinuation of Botulinum Toxin A Intradetrusor Injections for Neurogenic Detrusor Overactivity: A Multicenter Study.

PURPOSE: Data are lacking on long-term outcomes of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity. The aim of this study was to assess the outcomes of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity after more than 10 years of followup. MATERIALS AND METHODS: We retrospectively reviewed the charts of all consecutive neurological patients who had received onabotulinumtoxin A or abobotulinumtoxin A intradetrusor injections for neurogenic detrusor overactivity between January 2002 and November 2007 at a total of 3 academic centers. The primary outcome measure was the 10-year discontinuation rate. Other outcomes of interest were failure, reasons for discontinuation and subsequent treatments of neurogenic detrusor overactivity. Discontinuation-free and failure-free survival was estimated by Kaplan-Meier analyses. RESULTS: A total of 140 patients were included in study. The 10-year discontinuation-free and failure-free survival rates were 49.1% and 73%, respectively. The most common reason for discontinuation was failure in 43.7% of cases, which was primary and secondary in 17.2% and 26.5%, respectively. Secondary failure occurred after a median of 8 injections and a median of 80.1 months from the first injection. Other reasons for discontinuation were patient decision in 28.1% of patients, nonbotulinum toxin A related improvement of urinary incontinence in 14.1%, neurological condition progression in 12.5% and an adverse event in 1.6%. Discontinuation-free survival was significantly poorer in patients with spina bifida than in patients with multiple sclerosis or spinal cord injury (p = 0.02). CONCLUSIONS: More than half of the patients with neurogenic detrusor overactivity discontinued intradetrusor botulinum toxin A within the first 10 years after the initial injection. Patients with spina bifida are at high risk for discontinuation.

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.

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.

Assessment of a program to encourage the multidisciplinary management of urinary disorders in multiple sclerosis.

AIMS: Urinary disorders (UD) secondary to multiple sclerosis (MS) are common and can be responsible for complications. Since 2004, we organized in our region their management through a neuro-urological activity and a care network that established and distributed an algorithm for screening and first line care. The objective was to assess the effects of this organization on the management of UD and its impact for patients. METHODS: Between January 2004 and December 2009, 328 patients were seen in neuro-urological consultation. The data of a group of 168 patients consulting during the deployment of our organization (before January 2007: group 1) were compared to those of 160 patients taken when the organization was well established (from January 2007: group 2). In parallel, the modification of the prescription rate of the first-line examination patients was evaluated. RESULTS: The two groups were significantly different concerning age, duration of MS, EDSS score (Group 1 vs. Group 2 respectively 51.6 ± 12.6 vs. 48 ± 11.8 years, P = 0.008; 19 ± 9.7 vs. 13.8 ± 10.5 years, P < 0.0001; 5.8 ±2.0 vs. 5.1 ± 2.1, P = 0.008). The occurrence of urinary complications in group 1 was more frequent than in group 2 (66.3% vs. 40%, P < 0.0001). The rate of first-line examinations rose from 1/16 patient seen in January 2006 to 9/12 patients in January 2008. CONCLUSION: The multidisciplinary management of UD in MS led to patients being cared for sooner in the evolution of MS, with fewer complications and to an improvement in the rate of prescription of first-line examinations. Neurourol. Urodynam. 36:706-709, 2017. © 2016 Wiley Periodicals, Inc.

Intradetrusor injections of onabotulinum toxin A (Botox®) 300 U or 200 U versus abobotulinum toxin A (Dysport®) 750 U in the management of neurogenic detrusor overactivity: A case control study.

AIMS: To compare the outcomes of the first intradetrusor injections of abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with neurogenic detrusor overactivity (NDO). METHODS: A retrospective case-control study was conducted including 211 NDO patients treated in three consecutives eras with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients). Urodynamic and clinical parameters were compared between groups. The primary endpoint was the rates of success defined as the combination of urgency, urinary incontinence, and detrusor overactivity resolution. RESULTS: When comparing abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133), success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007) compared to those who received onabotulinum toxin 200 U. In contrast, there were similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between the first and the second injection in the onabotulinum toxin 300 U group (12.4 vs. 9.3 months; P = 0.09). CONCLUSIONS: Intradetrusor injections of abobotulinum toxin 750 U for NDO provided better outcomes than injections of onabotulinum toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300 U were similar but interval between injections tended to be longer with onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. © 2016 Wiley Periodicals, Inc.

Efficacy and safety of the first and repeated intradetrusor injections of abobotulinum toxin A 750 U for treating neurological detrusor overactivity.

PURPOSE: To assess clinical and urodynamic efficacy of the first and repeated intradetrusor injections of abobotulinum toxin A (Dysport(®), Ipsen(®), France) in patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic treatment. METHODS: A single-center retrospective study was conducted in 81 consecutive patients who had never received any botulinum toxin intradetrusor injections. They were treated with at least one 750 U intradetrusor injection of abobotulinum toxin A. All patients performed clean intermittent self-catheterization (CIC) before injections. Success was defined as a combination of no incontinence episode, a number of catheterization <8 reported in a 3-day bladder diary and the lack of detrusor overactivity. RESULTS: Six weeks after the first injection, the success rate was 64.2 %. The proportion of continent patients was 80.2 %, the mean number of CIC per 24 h reduced (-3.55, p < 0.0001) and the mean catheterization volume increased (+237.3 ml, p < 0.0001). Regarding urodynamics, mean maximum cystometric capacity and mean volume at the first uninhibited contraction increased (+132.7 ml, p < 0.0001 and +180 ml, p < 0.0001, respectively) and mean maximum bladder pressure decreased significantly (-21.5 cm H2O, p < 0.0001). Mean reinjection number was 3.9 and mean interval between reinjection was 8.8 ± 3 months. The clinical efficacy rate after each reinjection (up to fourteen) was at least 86.7 %. Out of 55 patients who underwent repeated injections, secondary resistance was noted in 2 (3.6 %). CONCLUSION: The results of the present study are in favor of a long-term safety and efficacy of abobotulinum toxin A 750 U for NDO.

Preliminary results of botulinum toxin A switch after first detrusor injection failure as a treatment of neurogenic detrusor overactivity.

AIMS: To assess the results of onabotulinum toxin detrusor injections when abobotulinum toxin detrusor injection failed. METHODS: Twenty-six patients, 15 women and 11 men, mean age 40.8 ± 12.7 years old, in whom a first injection of 750 U abobotulinum toxin in 20 sites failed in treating neurogenic detrusor overactivity, received onabotulinum toxin 300 U detrusor injections in 30 sites. Neurologic conditions were spinal cord injury in 14 cases, multiple sclerosis in nine, myelomeningocele in two and myelitis in one. Mean time between the two injections was 5.6 ± 1.4 months. Before and 6 weeks after each injection, patients carried out a 3-day bladder diary and had urodynamics. The success was defined as the combination of a clean intermittent self-catheterization number under 8 per 24 hr, urgency, urinary incontinence and detrusor overactivity relief. RESULTS: Out of 26 patients, the second injection was successful in 15 (57.7%). While the first injection of 750 U abobotulinum toxin had no impact at all, after 300 U onabotulinum toxin injection, the number of clean intermittent self-catheterization decreased significantly (11.3 ± 2.1 vs. 6.4 ± 1.9, P = 0.01), 17/26 (65.4%) patients achieved continence, urgency was relieved in 18/26 (69.2%) and detrusor overactivity in 15/26 (57.7%). CONCLUSIONS: In case of failure after a first detrusor injection of abobotulinum toxin, switching for onabotulinum toxin is efficient. Further investigations should be performed to assess whether the replacement of onabotulinum toxin by abobotulinum toxin provides the same results.