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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., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To describe the temporal development of and risk factors for the occurrence of unfavourable urodynamic parameters during the first year after spinal cord injury (SCI)., Patients and Methods: This population-based longitudinal study used data from 97 adult patients with a single-event traumatic or ischaemic SCI who underwent video-urodynamic investigation (UDI) at a university SCI centre. The first occurrences of unfavourable urodynamic parameters (detrusor overactivity combined with detrusor sphincter dyssynergia [DO-DSD], maximum storage detrusor pressure ≥40 cmH 2 O, bladder compliance <20 mL/cmH 2 O, vesico-ureteric reflux [VUR] and any unfavourable parameter [composite outcome]) were evaluated using time-to-event analysis., Results: The majority of the population (87/97 [90%]) had at least one unfavourable urodynamic parameter. Most unfavourable urodynamic parameters were initially identified during the 1- or 3-month UDI, including 92% of the DO-DSD (78/85), 82% of the maximum storage pressure ≥40 cmH 2 O (31/38), and 100% of the VUR (seven of seven) observations. No low bladder compliance was observed. The risk of DO-DSD was elevated in patients with thoracic SCI compared to those with lumbar SCI (adjusted hazard ratio [aHR] 2.38, 95% confidence interval [CI] 1.16-4.89). Risk of maximum storage detrusor pressure ≥40 cmH 2 O was higher in males than females (aHR 8.33, 95% CI 2.51-27.66), in patients with a cervical SCI compared to those with lumbar SCI (aHR 14.89, 95% CI 3.28-67.55), and in patients with AIS Grade B or C compared to AIS Grade D SCI (aHR 6.17, 95% CI 1.78-21.39). No risk factors were identified for the composite outcome of any unfavourable urodynamic parameter., Conclusions: The first UDI should take place within 3 months after SCI as to facilitate early diagnosis of unfavourable urodynamic parameters and timely treatment. Neuro-urological guidelines and individualised management strategies for patients with SCI may be strengthened by considering sex and SCI characteristics in the scheduling of UDIs., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation., Subjects/patients and Methods: We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12., Results: Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P < 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P < 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P < 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P > 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING., Conclusions: The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms., (© 2021 The Authors BJU International © 2021 BJU International.)

Study Design: Simulations using data from a prospective cohort study., Objectives: To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study., Setting: Spinal cord injury (SCI) rehabilitation centers in Switzerland., Methods: TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute SCI. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period., Results: The recruitment target of 114 patients is obtainable within the originally envisioned 3-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants., Conclusions: Prospective cohort data are a very valuable resource for planning RCTs., (© 2020. The Author(s), under exclusive licence to International Spinal Cord Society.)

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI., Methods and Analysis: TASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5-39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6-9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome., Ethics and Dissemination: TASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications., Trial Registration Number: NCT03965299., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To evaluate if urinary continence in patients with refractory neurogenic detrusor overactivity (NDO) incontinence after intradetrusor onabotulinumtoxinA injections is sufficient for appropriate outcome assessment or if urodynamic investigation (UDI) is needed., Patients and Methods: A consecutive series of 148 patients undergoing intradetrusor onabotulinumtoxinA injections for refractory NDO incontinence were prospectively evaluated. Patients underwent UDI before and at 6 weeks after onabotulinumtoxinA injections. The primary outcome was the prevalence of maximum storage detrusor pressure (Pdet max storage) of >40 cmH 2 O in continent patients at 6 weeks after treatment. The secondary outcomes were treatment effects on other clinical and video-urodynamic variables., Results: At 6 weeks after intradetrusor onabotulinumtoxinA injections, 98 of the 148 patients (66%) with NDO incontinence were continent. Of these patients, 18 (18%, confidence interval 12-27%) had a Pdet max storage of >40 cmH 2 O. Gender, underlying neurological disorder, and high Pdet max storage before treatment appear to increase the risk of poor urodynamic outcomes., Conclusions: Urinary continence is not sufficient for outcome assessment after intradetrusor onabotulinumtoxinA injections, as high intravesical pressures threatening the upper urinary tract may be missed in a relevant proportion of continent patients. Therefore, we strongly recommend UDI as a routine part of the follow-up., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) present with chronic bacteriuria. In these patients, antibiotic prophylaxis has been widely recommended since bacteriuria might impair treatment efficacy and cause urinary tract infections (UTI) but the evidence is limited. The aim of this study was to evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between 06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of 273 treatment cycles were prospectively evaluated. Before treatment urine samples were collected, patients with no clinical signs for UTI underwent onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria, respectively. Intradetrusor onabotulinumtoxinA injections were clinically and urodynamically successful in 70% (192/273). There was no association between bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23-1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95% CI 0.43-1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA injections, especially taking into account the alarming antibiotic resistance worldwide.

Background: Intradetrusor onabotulinumtoxinA (BoNT-ONA) injections have become a well-established therapy for refractory neurogenic detrusor overactivity (NDO). However, little is known about long-term outcome and patients' adherence to this treatment., Objective: To assess long-term outcomes of intradetrusor BoNT-ONA injections and patients' adherence to treatment., Design, Setting, and Participants: A consecutive series of 52 patients who underwent first intradetrusor BoNT-ONA injections for refractory NDO >10 yr ago were evaluated retrospectively and prospectively at a single university spinal cord injury (SCI) centre., Outcome Measurements and Statistical Analysis: Primary outcome was current neuro-urologic treatment. Secondary outcomes were urodynamic parameters. For data comparison, the paired/unpaired t test, chi-square test, and McNemar test were used., Results and Limitations: Mean duration since first intradetrusor BoNT-ONA injections was 12±2 yr. Most patients (61% [32 of 52]) suffered from SCI, 15% (8 of 52) from spina bifida, 14% (7 of 52) from multiple sclerosis (MS), and the remaining (10% [5 of 52]) from other neurologic disorders. Almost 60% (31 of 52) of all patients are continuing with intradetrusor BoNT-ONA injections but only 14% (1 of 7) of the patients with MS. Lack of clinical and/or urodynamic response (21% [11 of 52]) and switching to another treatment (antimuscarinics and/or neuromodulation) despite appropriate BoNT-ONA efficacy (19% [10 of 52]) were the reasons for discontinuation. In patients continuing BoNT-ONA treatment, the positive effect was sustained after repeat injections (p<0.05)., Conclusions: Although intradetrusor BoNT-ONA injections are a highly effective therapy for refractory NDO, approximately 40% of the patients discontinue treatment over time. All prospective neurologic patients should be given this information, and it needs to be considered in the treatment decision-making process., Patient Summary: Approximately 60% of the patients treated with intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity continue this therapy long term with good therapeutic effects., Study Registration Number: NCT01293110., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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 prospective 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 standardised questionnaires 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: ClinicalTrials.gov NCT01768910.