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STUDY DESIGN Prospective, multicenter, longitudinal cohort study. OBJECTIVES To describe female-male differences in first-line urological management during spinal cord injury (SCI) rehabilitation. SETTING Inpatient specialized post-acute SCI rehabilitation in Switzerland. METHODS Data on bladder storage medication (antimuscarinic and beta-3 agonist) use, suprapubic catheter placement, demographic and SCI characteristics was collected within 40 days of SCI and at rehabilitation discharge from May 2013-September 2021. Prevalence and indicators of bladder storage medication and suprapubic catheter use at discharge were investigated with sex-stratified descriptive and logistic regression analyses. RESULTS In 748 patients (219 females, 29%), bladder storage medication use at discharge had a prevalence of 24% (95% CI: 18-29%) for females and 30% (95% CI: 26-34%) for males and was indicated by cervical AIS grade A, B, C and traumatic SCI in both sexes. Thoracic AIS grade A, B, C SCI (males), and lumbar/sacral AIS grade A, B, C SCI (females) predicted higher odds of bladder storage medication use (SCI characteristic*sex interaction, p 60 in both sexes. Females with thoracic grade A, B, C SCI tended to have higher odds of suprapubic catheter use (SCI characteristic*sex interaction, p = 0.013). CONCLUSIONS We identified sex differences in urological management especially in persons with AIS grade C or higher sub-cervical SCI. There is scope for well-powered, female-specific research in SCI in order to understand the underlying mechanisms and support patient-tailored management.

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).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 cmHThe 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 cmHThe 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.

We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity.Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm HOne or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm HUsing a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

Summary Background Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. In the context of increasing antibiotic resistance, finding alternative treatments for UTIs is a top priority. We aimed to determine whether intravesical bacteriophage therapy with a commercial bacteriophage cocktail is effective in treating UTI. Methods We did a randomised, placebo-controlled, clinical trial, at the Alexander Tsulukidze National Centre of Urology, Tbilisi, Georgia. Men older than 18 years of age, who were scheduled for transurethral resection of the prostate (TURP), with complicated UTI or recurrent uncomplicated UTI but no signs of systemic infection, were allocated by block randomisation in a 1:1:1 ratio to receive intravesical Pyo bacteriophage (Pyophage; 20 mL) or intravesical placebo solution (20 mL) in a double-blind manner twice daily for 7 days, or systemically applied antibiotics (according to sensitivities) as an open-label standard-of-care comparator. Urine culture was taken via urinary catheter at the end of treatment (ie, day 7) or at withdrawal from the trial. The primary outcome was microbiological treatment response after 7 days of treatment, measured by urine culture; secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients having received at least one dose of the allocated treatment regimen. This trial is registered with ClinicalTrials.gov , NCT03140085 . Findings Between June 2, 2017, and Dec 14, 2018, 474 patients were screened for eligibility and 113 (24%) patients were randomly assigned to treatment (37 to Pyophage, 38 to placebo, and 38 to antibiotic treatment). 97 patients (28 Pyophage, 32 placebo, 37 antibiotics) received at least one dose of their allocated treatment and were included in the primary analysis. Treatment success rates did not differ between groups. Normalisation of urine culture was achieved in five (18%) of 28 patients in the Pyophage group compared with nine (28%) of 32 patients in the placebo group (odds ratio [OR] 1·60 [95% CI 0·45–5·71]; p=0·47) and 13 (35%) of 37 patients in the antibiotic group (2·66 [0·79–8·82]; p=0·11). Adverse events occurred in six (21%) of 28 patients in the Pyophage group compared with 13 (41%) of 32 patients in the placebo group (OR 0·36 [95% CI 0·11–1·17]; p=0·089) and 11 (30%) of 37 patients in the antibiotic group (0·66 [0·21–2·07]; p=0·47). Interpretation Intravesical bacteriophage therapy was non-inferior to standard-of-care antibiotic treatment, but was not superior to placebo bladder irrigation, in terms of efficacy or safety in treating UTIs in patients undergoing TURP. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a recognised or approved treatment option for UTIs, this trial provides new insight to optimise the design of further large-scale clinical studies to define the role of bacteriophages in UTI treatment. Funding Swiss Continence Foundation, the Swiss National Science Foundation, and the Swiss Agency for Development and Cooperation. Translations For the Georgian and German translations of the abstract see Supplementary Materials section.

Prospective, multicenter, longitudinal cohort study.To describe female-male differences in first-line urological management during spinal cord injury (SCI) rehabilitation.Inpatient specialized post-acute SCI rehabilitation in Switzerland.Data on bladder storage medication (antimuscarinic and beta-3 agonist) use, suprapubic catheter placement, demographic and SCI characteristics was collected within 40 days of SCI and at rehabilitation discharge from May 2013-September 2021. Prevalence and indicators of bladder storage medication and suprapubic catheter use at discharge were investigated with sex-stratified descriptive and logistic regression analyses.In 748 patients (219 females, 29%), bladder storage medication use at discharge had a prevalence of 24% (95% CI: 18-29%) for females and 30% (95% CI: 26-34%) for males and was indicated by cervical AIS grade A, B, C and traumatic SCI in both sexes. Thoracic AIS grade A, B, C SCI (males), and lumbar/sacral AIS grade A, B, C SCI (females) predicted higher odds of bladder storage medication use (SCI characteristic*sex interaction, p 0.01). Prevalence of suprapubic catheter use at discharge was 22% (95% CI: 17-28%) for females and 17% (95% CI: 14-20%) for males. Suprapubic catheter use was indicated by cervical AIS grade A, B, C SCI, and age60 in both sexes. Females with thoracic grade A, B, C SCI tended to have higher odds of suprapubic catheter use (SCI characteristic*sex interaction, p = 0.013).We identified sex differences in urological management especially in persons with AIS grade C or higher sub-cervical SCI. There is scope for well-powered, female-specific research in SCI in order to understand the underlying mechanisms and support patient-tailored management.

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 rehabilitation centers in Switzerland. Methods TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute spinal cord injury. 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 three-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.

OBJECTIVES: To identify factors influencing return for maintenance Percutaneous tibial nerve stimulation (PTNS) treatment after successful completion of a 12-week course of treatment for the overactive bladder (OAB). PATIENTS AND METHODS: Patients with OAB symptoms referred for PTNS treatment underwent twelve sessions of weekly PTNS treatment and evaluated at baseline and week 12 using the International Consultation on Incontinence Questionnaire on OAB (ICIQ-OAB), lower urinary tract symptoms related quality of life questionnaire (ICIQ-LUT symptoms QOL) and bladder diary (BD). Responders to treatment, evaluated using two patient-reported outcome measurements, were invited to return for maintenance treatments when symptoms returned. A PTNS Service Evaluation Questionnaire (PTNS-SEQ) was used to evaluate factors influencing return for maintenance treatment. RESULTS: 79 patients were evaluated (mean age 58.9 (±14.7), female 72.6%) and clustered into three groups - group 1 (n=28) did not respond to 12 weekly sessions of PTNS treatment; group 2 (n=28) responded to treatment but did not return for maintenance treatment and group 3 (n=31) responded to treatment and returned for maintenance treatment. There were no significant differences in demographic characteristics, diagnosis, baseline symptom scores and BD parameters between the three groups. Patients belonging to groups 2 and 3 experienced a significant improvement from baseline to week 12 in total OAB scores (group 2: -1.54 ± 1.85; group 3: -1.85 ± 2.28, p

To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation.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.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.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.

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.

Neuroimaging allows in vivo visualization of neuronal structures/processes to assess their involvement in bodily functions. This is particularly valuable for the assessment of complex, multilevel neuronal controlled functions, such as urine storage and micturition. Using positron emission tomography or functional magnetic resonance imaging, significant alterations of supraspinal lower urinary tract (LUT) control have been described in patients with neurogenic LUT dysfunction due to spinal cord injury, Parkinson's disease, and multiple sclerosis. Severity of such alterations often correlates with symptom/dysfunction severity, both of which could be partly mitigated by therapeutic interventions. However, the overall evidence and study quality are presently very limited, and a multidisciplinary approach will be required to achieve clinical relevance in the long term. PATIENT SUMMARY: We reviewed the findings of neuroimaging studies in patients with bladder dysfunction due to neurological trauma/disease. Changes in the nervous systems of these patients alter bladder control, and neuroimaging may become a valuable tool for assessing these alterations.

Background Tibial nerve stimulation (TNS) is an effective and safe treatment for idiopathic lower urinary tract dysfunction (LUTD), but its value in neurological patients is unclear. Objective To test the feasibility, acceptability, and safety of a randomized, sham-controlled, double-blind transcutaneous TNS (TTNS) setup for treating neurogenic LUTD. Design, setting, and participants A pilot study including nine patients with refractory neurogenic LUTD investigated prospectively at a university neuro-urology department. Intervention Randomized, sham-controlled, double-blind verum and sham TTNS was performed for 30 min twice a week, for 6 wks. Outcome measurements and statistical analysis Outcomes were feasibility, acceptability, and safety of the TTNS protocol. Secondarily, potential efficacy was investigated. Descriptive statistics were used. Results and limitations All procedures were feasible and well tolerated by all nine patients. Using verum TTNS, a motor response could be triggered in all patients and a sensory response in all but one. At the beginning and end of treatment, seven and six (78% and 67%) patients believed to receive verum TTNS, and five and six (56% and 67%) correctly guessed their group allocation, respectively. No treatment-related adverse events occurred. A comparison of baseline versus 6 wks of verum and sham TTNS led to relevant symptom and functional changes in only a limited number of piloted patients. Conclusions Verum and sham TTNS combined with the blinding procedures proved feasible and safe. Both interventions and procedures, as well as the randomization process, were well accepted by the patients. While the subsensory threshold TTNS approach in combination with the sham condition is advantageous for patients’ blinding, the clinical findings raised some doubt regarding sufficient TNS. Hence, relevant methodological adjustments concerning the adequate stimulation current and corresponding sham condition are needed before starting randomized controlled trials to clarify the value and role of TTNS in neuro-urology. Patient summary Transcutaneous tibial nerve stimulation is a promising treatment option for neurogenic lower urinary tract dysfunction, but methodological adjustments in treatment application are required before further prospective studies can be initiated.

Sexual dysfunction (SD) is common in multiple sclerosis (MS), however, under-reported. The aim of this study was to identify barriers faced by patients with MS and healthcare professionals (HCPs) in discussing SD. This was a two-part prospective study carried out at a tertiary care centre. Patients with MS were surveyed using a 29-item questionnaire and SD was assessed using the MSISQ and ASEX questionnaires; depression screened with PHQ-2. HCPs were surveyed using a 23-item questionnaire. Seventy four patients (mean age 42.4 ± 10.7, 54 females) and 98 HCPs (mean age 45.8 ± 8.9, 90 females) participated. SD was significant, with primary (36.4%), secondary (27%) and tertiary (29.8%) contributory factors. Commonest barriers reported by patients were dominance of neurological symptoms (N = 30, 40.5%), presence of family or friends (N = 28, 37.8%), and not being asked (N = 25, 33.8%), while HCPs reported presence of family or friends (N = 34, 34.7%), lack of knowledge about SD (N = 30, 30.6%), and inadequate time during the consultation (N = 27, 27.6%). Barriers to discussing SD are similar between patients and HCPs. The most common barriers are addressable through modifications in the clinic environment, raising awareness and providing training opportunities.

Percutaneous tibial nerve stimulation is a minimally invasive neuromodulation technique for treating overactive bladder symptoms. The aim of this study was to assess safety, efficacy and impact on quality of life of percutaneous tibial nerve stimulation in neurological patients reporting overactive bladder symptoms. In this retrospective evaluation over 18 months at a tertiary healthcare centre, patients finding first-line treatments for overactive bladder ineffective or intolerable underwent a standard 12-week course of percutaneous tibial nerve stimulation (Urgent PC, Uroplasty). Symptoms were evaluated using standardised International Consultation on Incontinence Questionnaires and bladder diaries. Of 74 patients (52 women, 22 men, mean age 56 years), 49 (66.2%) patients had neurological disorder [19 (25.7%) multiple sclerosis and 30 (40.5%) other neurological conditions] and 25 (33.8%) idiopathic overactive bladder. Overall for the entire cohort significant improvements were recorded after 12 weeks in the following domains: 24-h frequency on bladder diary − 1.67 (− 3.0, 0.33) (p = 0.002), number of incontinent episodes on bladder diary − 0.0 (− 1, 0) (p = 0.01), incontinence severity on bladder diary 0 (− 0.33, 0) (p = 0.007), OAB symptoms − 3 (− 11.5, 5) (p = 0.01), and quality of life − 16 (− 57, 6.5) (p = 0.004). There were no significant differences in outcomes between patients with idiopathic and neurogenic overactive bladder. Percutaneous tibial nerve stimulation appears to be a possible promising alternative for patients with neurological disorder reporting overactive bladder symptoms who find first-line treatments either ineffective or intolerable. However, a properly designed study is required to address safety and efficacy.

Background: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on the society is substantial. Moreover, the continuing increase of antibiotic resistance worldwide is alarming. We aimed to determine whether intravesical bacteriophage therapy is effective to treat UTI. Methods: In this randomised, placebo-controlled, double-blind clinical trial 97 patients presenting with UTI were enrolled to receive intravesical Pyo bacteriophage (n=28), intravesical placebo solution (n=32), or oral antibiotic therapy (n=37). The primary outcome included clinical and microbiological treatment response. Secondary outcomes included safety parameters and quantitative microbiological urine assessments. Findings: At day seven, the treatment success rates were statistically similar between the three groups: Compared to the Pyo bacteriophage (5/28 (18%)) group, the placebo group had 9/32 (28%) (Odds Ratio (OR) 1.8, 95% confidence interval (CI) 0.52-6.2; p=0.352) and the antibiotic group had 13/37 (35%) (OR 2.49, 95% CI 0.77-8.1; p=0.129) successes. Also, adverse events were statistically similar between the three groups. They were seen in 6/28 patients (21%) in the Pyo bacteriophage group, in 13/32 (41%) in the placebo group (OR 0.4, 95% CI 0.13-1.25; p=0.116) and in 11/37 (30%) in the antibiotic group (OR 0.65, 95% CI 0.21-2.03; p=0.452). Interpretation: Beside antibiotics, bacteriophages and bladder irrigation appear to have specific but limited beneficial effects on UTI control. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a valuable treatment option for UTIs, this randomized controlled trial provides new insights to optimize the setting for further large-scale clinical studies to define the role of bacteriophages for treating UTIs. Trial Registration: Trial registration number: ClinicalTrials.gov, number NCT03140085. Funding Statement: Swiss Continence Foundation (www.swisscontinencefoundation.ch) The Swiss National Science Foundation (www.snsf.ch) and the Swiss Agency for Development and Cooperation in the framework of the program SCOPES (Scientific cooperation between Eastern Europe and Switzerland, grant number 152304). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study protocol was approved by the institutional review board and ethical committee at TNCU (TNCU-02/283; Tbilisi, Georgia), complied with International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki.

AIMS Assessing the reliability of electrical pain threshold (PT) and evaluating the impact of stimulation frequency at different locations in the healthy lower urinary tract (LUT). METHODS Ninety subjects (age: 18.3-35.8 years, 40 females, 50 males) were randomly allocated to one stimulation site (bladder dome [BD], trigone, proximal, membranous (only males), or distal urethra). Using 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation (square wave, pulse width:1 ms), current perception thresholds (CPTs), PTs and tolerance thresholds were assessed at two visits. Analyses were performed using linear mixed models, intraclass correlation coefficients (ICC) and Bland-Altman method. RESULTS PTs vary in relation to stimulation frequency, location and between genders. PT decreased with higher stimulation frequency. The highest PTs were measured at the BD and membranous urethra with males reporting higher PTs than females. Reliability of PT assessments according to ICC was good to excellent across all frequencies, locations, and genders (ICC = 0.61-0.97), except for BD and distal urethra in females showing poor to fair reliability (BD: all frequencies, distal urethra: 0.5 Hz). CONCLUSIONS PTs can be safely and reliably assessed from bladder and urethral locations. Semi-objective PT assessment may provide additional information on functionality and sensitivity of the LUT slow fiber afferents and complement findings from urodynamic investigations and CPT assessments. In conclusion, the developed methodology may open new opportunities for using electrical stimulation paradigms for LUT PT assessments and diagnostics. All this allows a more precise, location-specific characterization of pain origin and pain reaction towards therapy.

Impaired lower urinary tract (LUT) afferents often cause LUT symptoms. Assessment of LUT afferent pathways is possible using bipolar cortical sensory evoked potential (SEP) recordings with the active electrode at the vertex during electrical stimulation in the LUT. This study aimed to investigate the topographical distribution and microstates of lower urinary tract sensory evoked potentials (LUTSEPs) using different stimulation frequencies. Ninety healthy subjects (18–36 years old, 40 women) were randomly assigned to one of five stimulation locations [bladder dome; trigone; proximal, membranous (men only) or distal urethra]. Cycles of 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation were applied using a custom-made catheter. Cortical activity was recorded from 64 surface electrodes. Marker setting was performed manually on an individual subject-level for the P1, N1, and P2 components of vertex recordings. N1 and P2 topographies presented with central negativities and positivities around the vertex. Regarding topographical distribution, Randomization Graphical User interface (RAGU) analyses revealed consistent frequency effects and microstates for N1/P2. Higher stimulation frequencies resulted in decreasing map strength for P1, N1, and P2. LUTSEP topographies suggest central generators in the somatosensory cortex, which are not detectable in a bipolar set-up. The observed frequency effect indicates fiber refractoriness at higher frequencies. The multichannel approach allows more comprehensive assessment of LUTSEPs and might therefore be sensitive to pathological changes. Examinations in patients with LUT symptoms are needed to further investigate this biomarker. Electronic supplementary material The online version of this article (10.1007/s10548-020-00796-z) contains supplementary material, which is available to authorized users.

Previous functional neuroimaging studies provided evidence for a specific supraspinal network involved in lower urinary tract (LUT) control. However, data on the reliability of blood oxygenation level-dependent (BOLD) signal changes during LUT task-related functional magnetic resonance imaging (fMRI) across separate measurements are lacking. Proof of the latter is crucial to evaluate whether fMRI can be used to assess supraspinal responses to LUT treatments. Therefore, we prospectively assessed task-specific supraspinal responses from 20 healthy participants undergoing two fMRI measurements (test-retest) within 5-8 weeks. The fMRI measurements, conducted in a 3T magnetic resonance (MR) scanner, comprised a block design of repetitive bladder filling and drainage using an automated MR-compatible and MR-synchronized infusion-drainage device. Following transurethral catheterization and bladder pre-filling with body warm saline until participants perceived a persistent desire to void (START condition), fMRI was recorded during repetitive blocks (each 15 s) of INFUSION and WITHDRAWAL of 100 mL body warm saline into respectively from the bladder. BOLD signal changes were calculated for INFUSION minus START. In addition to whole brain analysis, we assessed BOLD signal changes within multiple 'a priori' region of interest (ROI), i.e. brain areas known to be involved in the LUT control from previous literature. To evaluate reliability of the fMRI results between visits, we applied different types of analyses: coefficient of variation (CV), intraclass correlation coefficient (ICC), Sorensen-Dice index, Bland-Altman method, and block-wise BOLD signal comparison. All participants completed the study without adverse events. The desire to void was rated significantly higher for INFUSION compared to START or WITHDRAWAL at both measurements without any effect of visit. At whole brain level, significant (p

Objective To evaluate the applicability and precision of a novel infusion-drainage device (IDD) for standardised filling paradigms in neuro-urology and functional magnetic resonance imaging (fMRI) studies of lower urinary tract (LUT) (dys)function. Subjects/patients and methods The IDD is based on electrohydrostatic actuation which was previously proven feasible in a prototype setup. The current design includes hydraulic cylinders and a motorised slider to provide force and motion. Methodological aspects have been assessed in a technical application laboratory as well as in healthy subjects (n=33) and patients with LUT dysfunction (n=3) undergoing fMRI during bladder stimulation. After catheterisation, the bladder was pre-filled until a persistent desire to void was reported from each subject. The scan paradigm comprised of automated, repetitive bladder filling and withdrawal of 100 mL body warm (37° C) saline interleaved with rest and sensation rating. Neuroimaging data were analysed using Statistical Parametric Mapping 12. Results Volume delivery accuracy was between 99.1±1.2% and 99.9±0.2%, for different flowrates and volumes. MR compatibility was demonstrated with a small decrease in signal-to-noise ratio (SNR), i.e. 1.13% for anatomical and 0.54% for functional scans and a decrease of 1.76% for time-variant SNR. Automated, repetitive bladder filling elicited robust (p=0.05, family-wise error corrected) brain activity in areas previously reported to be involved in supraspinal LUT control. There was a high synchronism between the LUT stimulation and the blood oxygenation level dependent (BOLD) signal changes in such areas. Conclusion We were able to develop a magnetic resonance (MR) compatible and MR synchronised IDD to routinely stimulate the LUT during fMRI in a standardized manner. The device provides LUT stimulation at high system accuracy resulting in significant supraspinal BOLD signal changes in interoceptive and LUT control areas in congruence to the applied stimuli. The IDD is commercially available, portable, and multi-configurable. Such a device may help to improve precision and standardization of LUT tasks in neuroimaging studies on supraspinal LUT control, and may therefore facilitate multi-site studies and comparability between different LUT investigations in the future. This article is protected by copyright. All rights reserved.

Aims To evaluate the feasibility and reliability of current perception threshold (CPT) measurement for sensory assessment of distinct locations in the male lower urinary tract (LUT). Methods Twelve male subjects (>18 years) without LUT symptoms or medical comorbidities were eligible. CPTs were determined twice (interval: 7–20 days) at the bladder dome, trigone and the proximal, membranous, and distal urethra. Square wave electrical stimulation of 3 Hz/0.2 ms and 0.5 Hz/1 ms was applied using a transurethral 8F catheter placed under fluoroscopic control. Bladder volume was kept constant (60 mL) using a second 10F catheter. Repetitive measurements and reliability were assessed by analysis of variance (ANOVA) and intraclass correlation coefficient (ICC). Results The ANOVA revealed significant main effects for stimulation site (P = 0.008) and type of stimulation (P

Objectives To investigate feasibility, reproducibility and age dependency of sensory evoked cortical potentials (SEPs) after electrical stimulation of different locations in the lower urinary tract (LUT) in a cohort of middle-aged healthy women. Subjects and Methods In a group of 10 healthy middle-aged women [mean (sd) height 165 (5) cm and age 43 (6) years), electrical stimulation (0.5 and 3 Hz) was applied to the bladder dome, trigone, and proximal and distal urethra. SEPs were recorded at the Cz electrode with reference to Fz. All measurements were repeated three times with an interval of 3–5 weeks. Current perception thresholds (CPT), SEP latencies and amplitudes were analysed. Results were compared with a group of younger women published previously. Results LUT SEPs demonstrated two positive (P1, P2) and one negative peak (N1). The mean (sd) N1 latency was 108.9 (7.8), 116.2 (10.7), 113.2 (13.4) and 131.3 (35.6) ms for the bladder dome, trigone, proximal and distal urethra, respectively. N1 latencies, except for the distal urethra, were significantly shorter than those in younger women. Taking all data, i.e. young and middle-aged women, into account, there was a significant negative correlation between the variable age and CPT/dome (r = −0.462, P = 0.04) and N1 latency/dome (r = −0.605, P = 0.005) and a significant positive correlation between the variable age and N1P2 amplitude/dome (r = 0.542, P = 0.014). Conclusion LUT SEPs can be induced in middle-aged women with reliable N1 responses. Unexpectedly, N1 responses reveal a shortening with increasing age particularly when compared with younger women. Changes in sensory afferents may be explained by age-related qualitative reorganisations within the urothelium and suburothelium potentially altering afferent nerve excitability, which may have an impact on the development of non-neurological LUT symptoms (LUTS, e.g. overactive bladder) in women.

AIMS To assess the afferent innervation of various locations in the male lower urinary tract (LUT) using sensory evoked cortical potentials (SEPs). METHODS Twelve healthy men (mean age: 29.6 ± 7.2 years, mean height: 1.8 ± 0.1 m) underwent repetitive slow (0.5 Hz/1 ms) and fast (3 Hz/0.2 ms) electrical stimulations of bladder (dome/trigone) and urethral (proximal/membranous/distal) locations with simultaneous cortical SEP recording (Cz-Fz). Latencies (ms) and peak-to-peak amplitudes (μV) for SEP components P1, N1, and P2 were analyzed. Tibial SEPs were assessed as methodological control. The reproducibility was investigated from between visits and inter-rater assessments using Bland-Altman plots. Statistical tests comprised analysis of variance (ANOVA), linear regressions, and paired t-tests. Values are given as mean ± standard deviation. RESULTS Typical LUTSEPs with P1, N1, and P2 components were successfully detected (100% responder rate) for slow but less successfully for fast stimulation. The slow stimulation provided reproducible LUTSEPs with position specific N1 latencies: dome 125.6 ± 21.3 ms, trigone 122.9 ± 20.5 ms, proximal- 116.1 ± 21.4 ms, membraneous- 118.8 ± 29.3 ms, and distal urethra 108.8 ± 17.8 ms. Despite good inter-rater agreement, latency variability between and within subjects was higher for LUTSEPs than for tibial SEPs. N1 latencies became shorter (P

Background and purpose Magnetic resonance imaging (MRI)-derived spinal cord (SC) gray and white matter (GM/WM) volume are useful indirect measures of atrophy and neurodegeneration over time, typically obtained in the upper SC. Neuropathological evidence suggests that in certain neurological conditions, early degeneration may occur as low as the sacral SC. In this study, the feasibility of GM/WM segmentation of the conus medullaris (CM) was assessed in vivo. Methods Twenty-three healthy volunteers (11 female, mean age 47 years) underwent high-resolution 3T MRI of the CM using a 3-dimensional fast field echo sequence. Reproducibility of the volume measurements was assessed in 5 subjects (2 female, 25-37 years) by one rater who repeated the analysis 3 times and also with 2 additional raters working independently in order to calculate the intra- and interrater coefficient of variation (COV), respectively. Furthermore, the influence of age, gender, spine and SC metrics on tissue-specific measures of the CM was investigated. Results Volumetric CM analyses (N = 23) for the SC, GM, and WM revealed a mean (SD) total volume of CM-TV = 1746.9 (296.7) mm3 , CM-GM-TV = 731.2 (106.0) mm3 , and CM-WM-TV = 1014.6 (211.3) mm3 , respectively. The intra-rater COV for measuring the CM-TV and CM-GM-TV was 3.38% and 7.42%, respectively; the interrater COV was 3.43% and 10.80%, respectively. Using age, gender, spine and SC metrics in regression models substantially reduced group variability for CM-TV, CM-WM-TV, and CM-GM-TV by up to 39.2%, 42.7%, and 21.2%, respectively. Conclusions The results from this study demonstrate the feasibility of obtaining tissue-specific volume measurements in the CM by means of MRI with good reproducibility and provide normative data for future applications in neurological diseases affecting the lower SC.

Two types of biofeedback (BF), tomographic electroencephalogram (EEG) neurofeedback (NF) and electromyographic biofeedback (EMG-BF), both with phasic and tonic protocols, were compared for treatment effects and specificity in attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD trained their brain activity in the anterior cingulate cortex (ACC), and twelve trained activity of arm muscles involved in fine motor skills. In each training session, resting state 24-channel EEG and training performances were recorded. Both groups showed similar behavioral improvements and artifact reduction in selected conditions, with no significant advantages despite medium effect sizes on primary outcomes for NF. Only the EMG-BF group, however, showed clear improvement in training regulation performance, and specific motor coordination effects. The NF group tended to present individual normalization of trained frequency bands in the ACC during rest across training. The results provide evidence for some specific effects in our small sample, albeit only to a small extent.

Lower urinary tract symptoms are highly prevalent and a large proportion of these symptoms are known to be associated with a dysfunction of the afferent pathways. Diagnostic tools for an objective and reproducible assessment of afferent nerve function of the lower urinary tract are missing. Previous studies showed first feasibility results of sensory evoked potential recordings following electrical stimulation of the lower urinary tract in healthy subjects and patients. Nevertheless, a refinement of the methodology is necessary. This study is a prospective, randomized trial conducted at Balgrist University Hospital, Zurich, Switzerland. Ninety healthy subjects (forty females and fifty males) without lower urinary tract symptoms are planned to be included in the study. All subjects will undergo a screening visit (including standardized questionnaires, 3-day bladder diary, urinalysis, medical history taking, vital signs, physical examination, neuro-urological examination) followed by two measurement visits separated by an interval of 3 to 4 weeks. Electrical stimulations (0.5Hz-5Hz, bipolar, square wave, pulse width 1 ms) will be applied using a custom-made transurethral catheter at different locations of the lower urinary tract including bladder dome, trigone, proximal urethra, membranous urethra and distal urethra. Every subject will be randomly stimulated at one specific site of the lower urinary tract. Sensory evoked potentials (SEP) will be recorded using a 64-channel EEG cap. For an SEP segmental work-up we will place additional electrodes on the scalp (Cpz) and above the spine (C2 and L1). Visit two and three will be conducted identically for reliability assessment. The measurement of lower urinary tract SEPs elicited by electrical stimulation at different locations of the lower urinary tract has the potential to serve as a neurophysiological biomarker for lower urinary tract afferent nerve function in patients with lower urinary tract symptoms or disorders. For implementation of such a diagnostic tool into clinical practice, an optimized setup with efficient and reliable measurements and data acquisition is crucial. In addition, normative data from a larger cohort of healthy subjects would provide information on variability, potential confounding factors and cut-off values for investigations in patients with lower urinary tract dysfunction/symptoms. Clinicaltrials.gov; Identifier: NCT02272309 .

INTRODUCTION AND OBJECTIVES: Recent functional magnetic resonance imaging (fMRI) studies revealed supraspinal networks in response to bladder filling involved in perception and processing of bladder distension. However, reproducibility of blood-oxygenation-level dependent (BOLD) signal changes during bladder filling has not been proven yet. Therefore, our aim was to investigate BOLD signal changes in response to bladder filling to provide evidence for repeatability using a standardized filling paradigm, i.e. a magnetic resonance (MR)compatible and MR-synchronized infusion-drainage system. METHODS: 20 right-handed healthy subjects, 10 women and 10 men, mean age 39 years (range 22-54) with no history of urinary urgency and/or urinary incontinence were included. Visit 1: After catheterization and bladder pre-filling with body warm saline until persistent desire to void, we performed in a 3T MR scanner automated, repetitive bladder filling of 100mL body warm saline over 15s, i.e. block design study. Visit 2: Within 8 weeks from visit 1, a second MR scan was performed in the same manner. Using SPM8, BOLD signal changes during bladder filling were compared to rest, i.e. pre-filled condition. For within-group whole-brain (WB) analysis, a voxel-threshold was set at p

Objective Postural instability limits ambulatory capacity in patients with spinal cord injury (SCI). Galvanic vestibular stimulation (GVS) was used to investigate the integrity of vestibulospinal pathways and related changes in postural responses in SCI. Methods Binaural bipolar galvanic stimuli of 400 ms duration and 3 mA intensity were applied in 8 motor incomplete SCI and 8 control subjects who stood facing towards the left. EMG responses were recorded from the right soleus muscle and the trajectory of the centre of pressure (CoP) was measured with a force plate. Results There was no difference in excitability and amplitude of the responses between the groups. However, the latency and duration of the medium latency EMG response and all CoP responses were significantly longer in the SCI group. Additionally, postural stability was reduced in the SCI group, as shown by a greater tendency to fall due to GVS. Conclusions Despite early EMG responses proving the basic connectivity of the direct vestibulospinal pathways, the delayed GVS responses suggest a vestibulospinal deficit in the SCI subjects. Significance GVS can be applied in incomplete SCI to supplement the neurological examination by revealing changes in vestibulospinal responses and impairment of postural stability.

To evaluate the feasibility and reliability of current perception threshold (CPT) measurement for sensory assessment of distinct locations in the male lower urinary tract (LUT).Twelve male subjects (18 years) without LUT symptoms or medical comorbidities were eligible. CPTs were determined twice (interval: 7-20 days) at the bladder dome, trigone and the proximal, membranous, and distal urethra. Square wave electrical stimulation of 3 Hz/0.2 ms and 0.5 Hz/1 ms was applied using a transurethral 8F catheter placed under fluoroscopic control. Bladder volume was kept constant (60 mL) using a second 10F catheter. Repetitive measurements and reliability were assessed by analysis of variance (ANOVA) and intraclass correlation coefficient (ICC).The ANOVA revealed significant main effects for stimulation site (P = 0.008) and type of stimulation (P 0.001) with lower CPTs for 0.5 Hz/1 ms compared to 3 Hz/0.2 ms. There was no significant effect for visit number (P = 0.061). CPTs were higher for bladder dome than for proximal (0.5 Hz/1 ms: P = 0.022; 3 Hz/0.2 ms: P = 0.022) and distal urethra (0.5 Hz/1 ms: P = 0.026; 3 Hz/0.2 ms: P = 0.030). Reliability of CPT measurements was excellent to good (ICC = 0.67-0.96) except for the bladder dome (5 Hz/1 ms: ICC = 0.45; 3 Hz/0.2 ms: ICC = 0.20) and distal urethra (3 Hz/0.2 ms: ICC = 0.57).CPTs can be reliably detected at different LUT locations. However, alert and compliant subjects are essential. CPTs of LUT may become a complementary assessment method providing information on responsiveness and sensitivity of afferent LUT nerves. This is especially relevant for urethral afferents, which are not covered by standard urodynamic investigations. Neurourol. Urodynam. 36:469-473, 2017. © 2016 Wiley Periodicals, Inc.

INTRODUCTION AND OBJECTIVES: The control of the lower urinary tract (LUT) is a complex, multilevel process involving both the peripheral and central nervous system. Most patients with spinal cord injury (SCI) suffer from neurogenic LUT dysfunction and LUT symptoms severely impair the patients’ health-related quality of life. Although there are several concepts regarding neuronal control and perception in the normal and pathological LUT condition, the exact mechanisms involved remain to be elucidated. METHODS: In this functional magnetic resonance imaging (fMRI) study, we prospectively assessed 20 patients (mean age 43 years old, range 25e75) with cervical and thoracic SCI (12 with complete and 8 with incomplete lesion) suffering from neurogenic detrusor overactivity. All subjects underwent data acquisition in a 3 Tesla scanner. The scan paradigm (SP) comprised 3 different bladder stimulations: (1) repetitive bladder filling of 100mL body warm saline starting with an empty bladder, (2) repetitive infusion and withdrawal (100mL) of body warm saline starting with a pre-filled bladder and (3) repetitive bladder filling of 100mL cold saline. Date was analysed using SPM8. Second-level random effects group analysis (at a voxel-threshold of P

To investigate feasibility, reproducibility and age dependency of sensory evoked cortical potentials (SEPs) after electrical stimulation of different locations in the lower urinary tract (LUT) in a cohort of middle-aged healthy women.In a group of 10 healthy middle-aged women [mean (sd) height 165 (5) cm and age 43 (6) years), electrical stimulation (0.5 and 3 Hz) was applied to the bladder dome, trigone, and proximal and distal urethra. SEPs were recorded at the Cz electrode with reference to Fz. All measurements were repeated three times with an interval of 3-5 weeks. Current perception thresholds (CPT), SEP latencies and amplitudes were analysed. Results were compared with a group of younger women published previously.LUT SEPs demonstrated two positive (P1, P2) and one negative peak (N1). The mean (sd) N1 latency was 108.9 (7.8), 116.2 (10.7), 113.2 (13.4) and 131.3 (35.6) ms for the bladder dome, trigone, proximal and distal urethra, respectively. N1 latencies, except for the distal urethra, were significantly shorter than those in younger women. Taking all data, i.e. young and middle-aged women, into account, there was a significant negative correlation between the variable age and CPT/dome (r = -0.462, P = 0.04) and N1 latency/dome (r = -0.605, P = 0.005) and a significant positive correlation between the variable age and N1P2 amplitude/dome (r = 0.542, P = 0.014).LUT SEPs can be induced in middle-aged women with reliable N1 responses. Unexpectedly, N1 responses reveal a shortening with increasing age particularly when compared with younger women. Changes in sensory afferents may be explained by age-related qualitative reorganisations within the urothelium and suburothelium potentially altering afferent nerve excitability, which may have an impact on the development of non-neurological LUT symptoms (LUTS, e.g. overactive bladder) in women.

Frontal midline (fm-)theta activity has been related to working memory (WM) processes, as it typically increases with WM load. The robustness of this effect, however, varies across studies and subjects, putting limits to its interpretation. We hypothesized that variation in the fm-theta effect may reflect individual differences in task difficulty with increasing WM load as indicated by behavioural responses. We further tested whether effects in the alpha range are robust markers of WM load. We recorded 64-channel EEG from 24 healthy adults while they memorized either 2 or 4 unfamiliar symbols (low vs. high WM load) in a modified Sternberg task. The last 2 s of the retention phase were analyzed for WM load-related changes in the theta (5–7 Hz) and alpha range (lower: 8–10 Hz, upper: 10.5–12.5 Hz). Higher WM load led to less accurate and slower responses. The increase of fm-theta with WM load was most pronounced at fm electrodes, localized to anterior cingulate regions, and correlated with the participants’ decrease in accuracy due to higher WM load. Alpha peak frequency increased in the high compared to the low WM load condition, corresponding to a decrease in lower alpha range across all channels. The results demonstrate that previously reported variation in fm-theta workload effects can partly be explained by variation in task difficulty indexed by individual task accuracy. Moreover, the results also demonstrate that alpha WM load effects are prominent when separating upper and lower alpha., Brain Topography, 28 (1), ISSN:0896-0267, ISSN:1573-6792