Swine Pudendal Nerve as a Model for Neuromodulation Studies to Restore Lower Urinary Tract Dysfunction.

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the real-time need of the bladder. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimizing the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morphophysiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the fasciculate nature of the nerve and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Reliability Validity and Responsiveness of the Spinal Cord Independence Measure 4th Version in a Multicultural Setup.

OBJECTIVE: To examine the fourth version of the Spinal Cord Independence Measure for reliability and validity. DESIGN: Partly blinded comparison with the criterion standard Spinal Cord Independence Measure III, and between examiners and examinations. SETTING: A multicultural cohort from 19 spinal cord injury units in 11 countries. PARTICIPANTS: A total of 648 patients with spinal cord injury. INTERVENTION: Assessment with Spinal Cord Independence Measure (SCIM IV) and Spinal Cord Independence Measure (SCIM III) on admission to inpatient rehabilitation and before discharge. MAIN OUTCOME MEASURES: SCIM IV interrater reliability, internal consistency, correlation with and difference from SCIM III, and responsiveness. RESULTS: Total agreement between examiners was above 80% on most SCIM IV tasks. All Kappa coefficients were above 0.70 and statistically significant (P<.001). Pearson's coefficients of the correlation between the examiners were above 0.90, and intraclass correlation coefficients were above 0.90. Cronbach's alpha was above 0.96 for the entire SCIM IV, above 0.66 for the subscales, and usually decreased when an item was eliminated. Reliability values were lower for the subscale of respiration and sphincter management, and on admission than at discharge. SCIM IV and SCIM III mean values were very close, and the coefficients of Pearson correlation between them were 0.91-0.96 (P<.001). The responsiveness of SCIM IV was not significantly different from that of SCIM III in most of the comparisons. CONCLUSIONS: The validity, reliability, and responsiveness of SCIM IV, which was adjusted to assess specific patient conditions or situations that SCIM III does not address, and which includes more accurate definitions of certain scoring criteria, are very good and quite similar to those of SCIM III. SCIM IV can be used for clinical and research trials, including international multi-center studies, and its group scores can be compared with those of SCIM III.

Prevalence of nocturia after brain injury: a cross-sectional study in a single rehabilitation center.

Aim: to analyze the prevalence of nocturia and its possible neuro-urological correlations in patients with a history of acquired brain injury (ABI).Methods: a single-centre population-based prospective study involving outpatients who were previously admitted to our Rehabilitation Hospital for acute ABI ≥ 18 months and ≤2 years prior. Impact of nocturia on QoL was evaluated by the standardized International Consultation on Incotinence Nocturia Quality of Life (ICIQ N-QoL). All participants were given a three-day frequency chart. Probability value <0.05 was statistically significant.Results: 48/138 subjects (35%) showed nocturia at 2-year follow-up visit. No, significant differences in age, gender, duration of coma, state of consciousness, disability, cognitive impairment and stroke severity were found in patients with or without nocturia. Subarachnoid haemorrhage (ESA) was the main reason for ABI in subjects showing nocturia (p = .037). The overall ICIQ N-QOL score ranged from 12 to 50 (mean 30.12 ± 8.87). Of them, 75% showed a total score >26. Increased diurnal frequency and small bladder capacity was statistically significantly associated with nocturia (p < .05).Conclusions: the rate of nocturia 2 years following ABI was lower compared to other neurological populations, although it was significantly associated with other storage urinary symptoms.

An Inertial Measurement Unit-Based Wireless System for Shoulder Motion Assessment in Patients with Cervical Spinal Cord Injury: A Validation Pilot Study in a Clinical Setting.

Residual motion of upper limbs in individuals who experienced cervical spinal cord injury (CSCI) is vital to achieve functional independence. Several interventions were developed to restore shoulder range of motion (ROM) in CSCI patients. However, shoulder ROM assessment in clinical practice is commonly limited to use of a simple goniometer. Conventional goniometric measurements are operator-dependent and require significant time and effort. Therefore, innovative technology for supporting medical personnel in objectively and reliably measuring the efficacy of treatments for shoulder ROM in CSCI patients would be extremely desirable. This study evaluated the validity of a customized wireless wearable sensors (Inertial Measurement Units-IMUs) system for shoulder ROM assessment in CSCI patients in clinical setting. Eight CSCI patients and eight healthy controls performed four shoulder movements (forward flexion, abduction, and internal and external rotation) with dominant arm. Every movement was evaluated with a goniometer by different testers and with the IMU system at the same time. Validity was evaluated by comparing IMUs and goniometer measurements using Intraclass Correlation Coefficient (ICC) and Limits of Agreement (LOA). inter-tester reliability of IMUs and goniometer measurements was also investigated. Preliminary results provide essential information on the accuracy of the proposed wireless wearable sensors system in acquiring objective measurements of the shoulder movements in CSCI patients.

Italian electronic personal assessment questionnaire-pelvic floor (I.ePAQ-PF): Psychometric validation of the urinary section.

AIM: Tools for remote clinical assessment have become increasingly important. Patient-reported outcome questionnaires are increasingly being considered as the keystones of pelvic floor disorder assessment. An innovative English language multidisciplinary electronic Personal Assessment Questionnaire (ePAQ-PF) was psychometrically validated in 2006. A certified Italian version (I.ePAQ-PF) has been recently made available by the Italian Society of Urodynamics. In this study, we aimed to test the psychometric properties to validate the urinary dimension of the I.ePAQ-PF. METHODS: Women complaining of lower urinary tract symptoms were enrolled. After providing informed consent, women filled in the I.ePAQ-PF via a dedicated touch-screen display (T0), together with concurrent questionnaires: International Consultation on Incontinence Questionnaire-Short form, Urgency Severity Scale, Urogenital Distress Inventory, and Patient Global Impression of Improvement. Cronbach's α and Spearman's correlation coefficients were adopted (validity). A test-retest was performed in 47 cases (reliability), and the intraclass correlation coefficient (ICC) was analyzed. I.ePAQ-PF was also administered after treatment (T1) and compared with baseline data via a Wilcoxon's test and Cohen's effect-size tests (responsiveness). RESULTS: Ninety-three women were included. Internal consistency was confirmed (Cronbach's α >.7). A Spearman's correlation test showed a good correlation (>0.6) between I.ePAQ-PF and conceptually similar questionnaires. I.ePAQ-PF seems to be highly reproducible in all domains (ICC >0.86). The questionnaire scored significantly differently (Wilcoxon test P < .003) in all domains after the treatment. Responsiveness was further confirmed by Cohen's effect size of more than 30%. CONCLUSIONS: The Italian ePAQ-PF (urinary domain) fully satisfies the psychometric properties of validity, reliability, and responsiveness and is ready for clinical application in Italian clinical settings.

Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies.

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra-sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti-muscarinic drugs; secondly, in intra-vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra-cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti-inflammatory treatment could positively influence the disease fate.

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury.

Spinal cord injury (SCI) usually affects younger age groups with male preponderance. The most common traumatic cause is road traffic accident followed by sports accidents and gun-shot injuries. Infections and vascular events make up non-traumatic causes. There is regional variance in incidence and prevalence of SCI. Most systematic reviews have been undertaken from USA, Canada, and Australia with only few from Asia with resultant difficulty in estimation of worldwide figures. Overall, the incidence varies from 12 to more than 65 cases/million per year. The first peak is in young men between 15 and 29 years and second peak in older adults. The average age at injury is 40 years, with commonest injury being incomplete tetraplegia followed by complete paraplegia, complete tetraplegia, and incomplete paraplegia. The bladder function is reliant on both central and peripheral nervous systems for co-ordination of storage and voiding phases. The pathophysiology of bladder dysfunction can be described as an alteration in micturition reflex. It is postulated that a new spinal reflex circuit develops which is mediated by C fibers as response to reorganization of synaptic connections in spinal cord. This is responsible for the development of neurogenic detrusor overactivity (NDO). Various neurotrophic hormones like nerve growth factor affect the morphological and physiological changes of the bladder afferent neurons leading to neuropathic bladder dysfunction. A suprasacral SCI usually results in a voiding pattern consistent with NDO and sphincter dyssynergia. Injury to either the sacral cord or cauda equina results in detrusor hypoactivity/areflexia with sphincter weakness.

Adolescence transitional care in neurogenic detrusor overactivity and the use of OnabotulinumtoxinA: A clinical algorithm from an Italian consensus statement.

AIMS: OnabotulinumtoxinA (onaBNTa) for treating neurogenic detrusor overactivity (NDO) is widely used after its regulatory approval in adults. Although the administration of onaBNTa is still considered off-label in children, data have already been reported on its efficacy and safety. Nowadays, there is a lack of standardized protocols for treatment of NDO with onaBNTa in adolescent patients in their transition from the childhood to the adult age. With the aim to address this issue a consensus panel was obtained. METHODS: A panel of leading urologists and urogynaecologists skilled in functional urology, neuro-urology, urogynaecology, and pediatric urology participated in a consensus-forming project using a Delphi method to reach national consensus on NDO-onaBNTa treatment in adolescence transitional care. RESULTS: In total, 11 experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥70% of the experts agreed on recommendations. To facilitate a common understanding among all experts, a face-to-face consensus meeting was held in Rome in march 2015 and then with a follow-up teleconference in march 2017. By the end of the Delphi process, formal consensus was achieved for 100% of the items and an algorithm was then developed. CONCLUSIONS: This manuscript represents the first report on the onaBNTa in adolescents. Young adults should be treated as a distinct sub-population in policy, planning, programming, and research, as strongly sustained by national public health care. This consensus and the algorithm could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.

Heterogeneity in reporting on urinary outcome and cure after surgical interventions for stress urinary incontinence in adult neuro-urological patients: A systematic review.

AIMS: To describe all outcome parameters and definitions of cure used to report on outcome of surgical interventions for stress urinary incontinence (SUI) in neuro-urological (NU) patients. METHODS: This systematic review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The study protocol was registered and published (CRD42016033303; http://www.crd.york.ac.uk/PROSPERO). Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov were systematically searched for relevant publications until February 2017. RESULTS: A total of 3168 abstracts were screened. Seventeen studies reporting on SUI surgeries in NU patients were included. Sixteen different outcome parameters and nine definitions of cure were used. Six studies reported on objective outcome parameters mainly derived from urodynamic investigations. All studies reported on one or more subjective outcome parameters. Patient-reported pad use (reported during interview) was the most commonly used outcome parameter. Only three of 17 studies used standardized questionnaires (two on impact of incontinence and one on quality of life). Overall, a high risk of bias was found. CONCLUSIONS: We found a considerable heterogeneity in outcome parameters and definitions of cure used to report on outcome of surgical interventions for SUI in NU patients. The results of this systematic review may begin the dialogue to a future consensus on this topic. Standardization of outcome parameters and definitions of cure would enable researchers and clinicians to consistently compare outcomes of different studies and therapies.

Value of urodynamic findings in predicting upper urinary tract damage in neuro-urological patients: A systematic review.

AIM: The main goals of neurogenic lower urinary tract dysfunction (NLUTD) management are preventing upper urinary tract damage (UUTD), improving continence, and quality of life. Here, we aimed to systematically assess all available evidence on urodynamics predicting UUTD in patients with NLUTD. METHODS: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed in March 2017. Only neuro-urological patients assessed by urodynamics were included. Any outcome of upper urinary tract function were evaluated. RESULTS: Forty-nine studies (1 randomized controlled trial, 9 prospective, and 39 retrospective case series) reported urodynamic data on 4930 neuro-urological patients. Of those, 2828 (98%) were spina bifida (SB) children. The total number of adults was 2044, mainly having spinal cord injury (SCI) (60%). A low bladder compliance was found in 568 (46.3%) and 341 (29.3%) of the paediatric and adult population, respectively. Hydronephrosis (HDN) was detected in 557 children (27.8%) in 19/28 studies and 178 adults (14.6%), mainly SCI, in 14/21 studies. Nine out of 30 multiple sclerosis (MS) patients affected by HDN (16.8%) showed low compliance in 4/14 studies. CONCLUSIONS: Patients with SB and SCI have a higher risk of developing UUTD (mainly reported as HDN) compared to those with MS. Reduced compliance and high DLPP were major risk factors for UUTD. Although our findings clarify the mandatory role of urodynamics in the management of NLUTD, standardization and better implementation of assessments in daily practice may further improve outcomes of neuro-urological patients based on objective measurements, that is, urodynamics.

Recurrent bacterial symptomatic cystitis: A pilot study on a new natural option for treatment.

OBJECTIVES: The aim of our study was to explore the effectiveness of the combination of D-mannose, Salicin, and Lactobacillus acidophilus (La-14) in patients complaining recurrent symptomatic cystitis due to E. coli. MATERIALS AND METHODS: From July 2013 to September 2014, 85 consecutive subjects (68 women and 17 men) affected by recurrent symptomatic cystitis were enrolled. Of those, 46 (33 women and 13 men) suffered from neurogenic bladder. Overall 78 patients received an initial 5-days regimen consisting on a tid oral combination of 1000 mg of D-mannose plus 200 mg of dry willow extract (salicin) (attack phase), followed by bid 7-days with 700 mg of D-mannose plus 50 mg (1x109 CFU) of Lactobacillus acidophilus (La-14) (maintenance treatment). The maintenance treatment was repeated every 15 days for the next two months. Patients' symptoms were evaluated through a 3-days bladder diary and a Visual Analogic Scale (VAS). RESULTS: After treatment VAS scores decreased from 8.07 ± 1.70 to 4.74 ± 2.07 (p = 0.001) in non-neurological patients (group A) and from 7.21 ± 1.90 to 3.74 ± 3.12 (p = 0.001) in the neurological patients (group B). A significant reduction of daily frequency was noted in both groups: from 14 ± 3 to 7 ± 3 (p = 0.001) in group A and from 15 ± 3 to 8 ± 3 (p = 0.001) in group B. A reduction of incontinence episodes in Group A patients was observed, as well as in 12/39 Group B. Improvements were maintained during follow-up. CONCLUSION: This therapeutic approach combining D-Mannose with Salicin (acute treatment) and Lactobacillus acidophilus La-14 (maintaining treatment) seems to be effective in symptomatic bacterial UTIs. Further larger and randomized control trials (RCTs) are needed to confirm our results.

Real-life clinical practice of onabotulinum toxin A intravesical injections for overactive bladder wet: an Italian consensus statement.

PURPOSE: We developed a consensus on best practice in the real-life management of patients with overactive bladder (OAB) with onabotulinumtoxin A (Onabot/A). METHODS: In March 2015, an interdisciplinary conference was convened. Eleven panelists were invited to review the literature, to present their personal experience and to respond to a number of questions from: "when do we propose Onabot/A treatment" to "when do you decide to re-inject a patient?" A summary of findings of the meeting was provided to all panelists for review and approval. RESULTS: The following statements were agreed. Refractory OAB can be defined based on lack of adherence to first- and second-line treatments for OAB regardless of the underlying cause. Onabot/A treatment can be proposed to refractory OAB patients provided they are willing to perform intermittent catheterization if needed. Before treatment, uroflowmetry with post-void residual evaluation is needed to rule out voiding dysfunction, while urodynamics should be done in cases of complicated OAB wet. Urinary tract infection should be ruled out or treated before the injection. The injection can be performed in the endoscopy room, in an out-patient basis, with local anesthesia. Antibiotic prophylaxis should be initiated with oral drugs. A first follow-up visit should be planned 10-15 days after treatment and residual urine checked. Retreatment can be decided on patients' request, when symptoms worsen. CONCLUSIONS: This consensus document provides a guide for the management of refractory OAB patients with Onabot/A in real life. A number of questions about the effectiveness of Onabot/A in real life remain open.

Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study.

AIMS: Assess the efficacy and safety of abobotulinumtoxinA (Dysport®) in adult patients with neurogenic detrusor overactivity (NDO). METHODS: This Phase IIa, international, multicentre, double-blind, randomised, placebo controlled, pilot study enrolled 47 patients with NDO and urinary incontinence resulting from spinal cord injury (SCI) or multiple sclerosis (MS). Patients were treated with 15 intra-detrusor injections of Dysport 750 U or the equivalent placebo (n = 16 and 7) or 30 injections of Dysport 750 U or the equivalent placebo (n = 17 and 7). Primary endpoint was change from baseline in mean number of daily incontinence episode frequency (IEF) at day 84. Secondary endpoints included change from baseline in urodynamic parameters and quality of life (QOL). A safety assessment was also conducted. RESULTS: Adjusted mean changes from baseline in IEF were -3.2 (-76%) and -1.7 (-15%) for 15 injections Dysport and placebo groups, respectively, (P = 0.1103) and -3.2 (-88%) and -2.6 (-73%) for 30 injections Dysport and placebo groups, respectively, (P = 0.0686). Statistically significant improvements in maximum cystometric capacity, maximum detrusor pressure and volume at first contraction were reported in the Dysport groups compared with placebo (P < 0.05). Improvements in QOL were reported. Three muscle weakness episodes were reported as serious adverse events in two tetraplegic and one paraplegic patient, all in the 15 injections Dysport group. CONCLUSIONS: Both 15 and 30 injections administration modes of Dysport decreased daily IEF and resulted in significant improvements in urodynamic parameters in NDO patients with MS or SCI. Reduction to 15 injection sites did not appear to be associated with any impact on efficacy. Neurourol. Urodynam. 36:457-462, 2017. © 2016 Wiley Periodicals, Inc.

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long-term extension study.

AIMS: To present final efficacy/safety results from a prospective, long-term extension trial of onabotulinumtoxinA for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO); patients received treatment for up to 4 years. METHODS: Patients who completed a 52-week, phase III trial of onabotulinumtoxinA for NDO were eligible to enter a 3-year, multicenter, open-label extension study of intradetrusor onabotulinumtoxinA (200U or 300U). Patients were treated "as needed" based on their request and fulfillment of prespecified qualification criteria (≥12 weeks since previous treatment and a UI episode threshold). Assessments included change from study baseline in UI episodes/day (primary efficacy measure), volume/void, and Incontinence Quality of Life (I-QOL) total score (week 6); duration of effect; adverse events (AEs); and initiation of de novo clean intermittent catheterization (CIC). Data are presented for up to six treatments. RESULTS: OnabotulinumtoxinA 200U consistently reduced UI episodes/day; reductions from baseline ranged from -3.2 to -4.1 across six treatments. Volume/void consistently increased, nearly doubling after treatment. I-QOL improvements were consistently greater than twice the minimally important difference (+11 points). Overall median duration of effect was 9.0 months (200U). Results were similar for onabotulinumtoxinA 300U. Most common AEs were urinary tract infections and urinary retention. De novo CIC rates were 29.5, 3.4, and 6.0% (200U), and 43.0, 15.0, and 4.8% (300U) for treatments 1-3, respectively; de novo CIC rates were 0% for treatments 4-6. CONCLUSIONS: OnabotulinumtoxinA treatments consistently improve UI, volume/void, and QOL in patients with UI due to NDO in this 4-year study, with no new safety signals. Neurourol. Urodynam. 36:368-375, 2017. © 2015 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Continent catheterizable tubes/stomas in adult neuro-urological patients: A systematic review.

AIMS: To systematically review all available evidence on the effectiveness and complications of continent cutaneous stoma or tube (CCS/T) to treat bladder-emptying difficulties in adult neuro-urological patients. METHODS: The search strategy and studies selection were performed on Medline, Embase, and Cochrane using the PICOS method according to the PRISMA statement (CRD42015019212; http://www.crd.york.ac.uk/PROSPERO). RESULTS: After screening 3,634 abstracts, 11 studies (all retrospective, enrolling 213 patients) were included in a narrative synthesis. Mean follow-up ranged from 21.6 months to 8.7 years (median: 36 months, IQR 28.5-44). At last follow-up, the ability to catheterize rate was ≥84% (except in one study: 58.3%) and the continence rate at stoma was >75%. Data comparing health-related quality-of-life before and after surgery were not available in any study. Overall, 85/213 postoperative events required reoperation: 7 events (7 patients) occurring ≤3 months postoperatively, 22 events (16 patients) >3 months, and 56 events (55 patients) for which the time after surgery was not specified. Sixty additional complications (60 patients) were reported but did not require surgical treatment. Tube stenosis occurred in 4-32% of the cases (median: 14%, IQR 9-24). Complications related to concomitant procedures (augmentation cystoplasty, pouch) included neovesicocutaneous fistulae, bladder stones, and bladder perforations. Risk of bias and confounding was high in all studies. CONCLUSIONS: CCS/T appears to be an effective treatment option in adult neuro-urological patients unable to perform intermittent self-catheterization through the urethra. However, the complication rate is meaningful and the quality of evidence is low, especially in terms of long-term outcomes including the impact on the quality-of-life.

Long-term effectiveness and complication rates of bladder augmentation in patients with neurogenic bladder dysfunction: A systematic review.

AIMS: To systematically evaluate effectiveness and safety of bladder augmentation for adult neuro-urological patients. METHODS: The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement was followed for review of publications. The Medline, Embase, and Cochrane controlled trial databases and clinicaltrial.gov were searched until January 2015. No limitations were placed on date or language. Non-original articles, conference abstracts, and publications involving children and animals were excluded. Risk-of-bias and confounder assessment was performed. RESULTS: A total of 20 studies including 511 patients were eligible for inclusion. The level of evidence for the included studies was low, most level 4 studies with only one level 3 study. The data were narratively synthesized. Across all studies high risk-of bias and confounding was found. Primary outcomes were assessed in 16 of the 20 studies and showed improved quality of life and anatomical changes as well as stable renal function. The secondary outcomes were reported in 17 of the 20 studies and urodynamic parameters and continence all demonstrated improvement after bladder reconstruction. Long-term complications continued up to 10 years post-operatively, including bowel dysfunction in 15% of the patients, stone formation in 10%, five bladder perforations and one bladder cancer. CONCLUSIONS: Available studies are not plentiful and of relatively poor quality, appropriately designed prospective studies are urgently needed. Despite this, bladder augmentation appears to be a highly effective procedure at protecting the upper urinary tract and improving quality of life. However, it is associated with relatively high morbidity in both the short and long term.

Long-term response of different Botulinum toxins in refractory neurogenic detrusor overactivity due to spinal cord injury.

PURPOSE: To assess the response in spinal cord injured patients alternatively treated with different types and dosages of Botulinum neurotoxin type A (BoNT/A) over 15 years. MATERIAL AND METHODS: Patients who underwent first BoNT/A from 1999-2001 and practiced intermittent catheterization were included. Baseline 3-day bladder diary (BD) and urodynamics were collected. BoNT/A failure was defined when patients asked for re-injection ≤ 3 months post-treatment. Criteria for re-injection was at least one daily episode of urinary incontinence at BD. Before re-injection, patients were asked if they had reached 6 months of dryness without antimuscarinics (YES response). RESULTS: Overall, 32/60 (53.4%) "No failure" (NF) group; 16 (26.6%) "occasional failure" (OF) and 12 (20%) "consecutive failure" (CF) were included. A total of 822 BoNT/A infiltrations were performed. The mean interval from previous injection to treatment re-scheduling was 8 months. No significant differences between treatments were found within the three groups (p>0.05). The percentage of YES responses increased from 19% (AboBoNT/A 500IU) to 29 % (OnaBoNT/A 300IU) in NF, and from 18% (AboBoNT/A 500IU) to 25% (OnaBoNT/A 300IU) for OF. Five NF cases (15.6%) maintained 6 months of dryness after each injection. Among the baseline variables, only low compliance (< 20mL/cmH2O) was found as predictor for failure (p=0.006). CONCLUSIONS: Long term BoNT/A for NDO did not increase failures, independent of the types of treatments and switching. Definition of failure and other criteria for continuing repetitive BoNT/A treatment is mandatory. CF was predictable for no response in earlier follow-up.