Lorenz Leitner

Urodynamic Investigation: A Valid Tool to Define Normal Lower Urinary Tract Function?

Objectives To evaluate whether urodynamic investigation (UDI), the gold standard to assess refractory lower urinary tract symptoms (LUTS), is appropriate to select healthy volunteers with apparent normal lower urinary tract function as control subjects for comparative studies. Subjects and Methods 42 healthy subjects (22 women, mean age 32±10 years; 20 men, mean age 37±12 years) without LUTS were included into this prospective single-centre cohort study. All subjects recorded a 3-day bladder diary, completed validated questionnaires regarding LUTS, and underwent neuro-urological assessment as well as free uroflowmetry. Same session repeat UDI was performed according to “Good Urodynamic Practice” recommended by the International Continence Society, but using an air-charged instead of a water-filled catheter, and evaluated by a blinded investigator. Results All 3-day bladder diaries, LUTS questionnaires, neuro-urological assessments and free uroflowmetries were within normal limits. Overall (either during the first or second UDI), same session repeat UDI revealed pathological findings in 71% (30/42): Detrusor overactivity was detected in 14% (3/22) and 30% (6/20), post void residual >100mL in 14% (3/22) and 25% (5/20), bladder outlet obstruction in 9% (2/22) and 20% (4/20) and detrusor sphincter dyssynergia in 77% (17/22) and 65% (13/20) of our women and men, respectively. Repeatability of detrusor overactivity (κ = 0.78, 95% CI: 0.54–1.02) and detrusor sphincter dyssynergia (κ = 0.77, 95% CI: 0.55–0.98) showed substantial agreement between both UDIs. All other assessed urodynamic parameters had wide 95% limits of agreement for differences in the parameters indicating poor repeatability. Conclusions More than 70% of our healthy subjects showed pathological urodynamic findings. Although UDI is the gold standard to assess refractory LUTS, it seems not to be applicable in healthy subjects to define normal lower urinary tract function. Therefore, we do not recommend using UDI to select healthy control subjects.

Prediction of autonomic dysreflexia during urodynamics: a prospective cohort study

BackgroundAutonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation.MethodsThis prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation.ResultsWe found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2–9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4–4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8–11.7, and AOR 2.2, 95% CI 1.1–4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1–C4 (AOR 16.2, 95% CI 5.9–57.9) to T4–T6 (AOR 2.6, 95% CI 1.3–5.2), compared to lesions at T7 or below.ConclusionsIn patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications.Trial registrationClinicalTrials.gov, NCT01293110.

A novel infusion-drainage device to assess lower urinary tract function in neuro-imaging.

To evaluate the applicability and precision of a novel infusion‐drainage device (IDD) for standardized filling paradigms in neuro‐urology and functional magnetic resonance imaging (fMRI) studies of lower urinary tract (LUT) function/dysfunction.

Antibiotic prophylaxis may not be necessary in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections for neurogenic detrusor overactivity.

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.

Adapted Bacteriophages for Treating Urinary Tract Infections

Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥104 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option.

PD70-10 ABNORMAL RESTING-STATE INTER-NETWORK COUPLING IN PATIENTS WITH NON-NEUROGENIC OAB

INTRODUCTION AND OBJECTIVES: Recent fMRI studies using bladder filling tasks demonstrated alterations in supraspinal LUT control networks (NT) in women with OAB, particularly regarding NT connectivity and white matter changes. It is unclear if patients with OAB show altered supraspinal responses during empty bladder conditions and if resting-state (RS) activity is altered by catheterization usually require for bladder filling tasks. We applied a functionally-motivated NT approach, using RS functional NT connectivity (RS-FNC) analysis, to examine RS related NT interactions in age-matched controls and OAB patients. Based on previous publications we hypothesize lower FNC in OAB patients. METHODS: We examined 10 healthy females (37 9y) and 10 with OAB (38 8y) and DO in urodynamics. For RS-fMRI whole brain images, using a multi-slice EPI sequence were acquired in a 3T scanner. Using SPM8, we estimated the RS NTs using the GIFT toolbox and independent component analysis (ICA) across all subjects. IC dimension estimation was performed using the minimum description length criteria, modified to account for spatial correlation. All nonneuronal ICs (e.g. cardiac-induced pulsatile artifact and head motion) were removed, resulting in a total of 9 neuronal ICs (including the default mode NT, DMN). Prior to FNC analysis, IC time courses were bandpass (0.013 Hz & 0.24 Hz). Group differences in FNC strength were calculated using the FNC toolbox for both conditions. The temporal lags between ICA-derived NTs were computed to gain directed FNC. Significant between-group FNC (and lag) results are shown at p < 0.05 FDR corrected. RESULTS: Healthy controls showed significantly higher (directed) FNC than OAB patients for: DMN (left-dominant) / DMN (right-dominant) and fronto-parietal attention NT / DMN (left-dominant). OAB patients show lower inter-networkcoupling, especially between the DMN(IC1) and the left-dominant fronto-parietal attention NT (FPN,IC4). Further, FNC differed between groups in temporal synchronicity. E.g., lag time between the DMN and FPN is shorter than between the right and left DMN in OAB patients. CONCLUSIONS: We conclude that the interplay between neuronal NTs is altered in OAB patients compared to healthy subjects already during RS. Aberrant coupling of the fronto-parietal attention NT might indicate a general neuronal deficit that impairs adequate LUT control, i.e. suppression of premature micturition reflex, consequently resulting in OAB and incontinence. These novel findings can be an important link to the underlying pathophysiology of OAB in otherwise neurological unimpaired patients.

Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: Do we need urodynamic investigation for outcome assessment?

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.

MP17-15 BACTERIURIA IN PATIENTS UNDERGOING INTRADETRUSOR ONABOTULINUMTOXINA INJECTIONS FOR REFRACTORY NEUROGENIC DETRUSOR OVERACTIVITY: DO WE NEED ANTIBIOTIC PROPHYLAXIS?

Leitner L1, Sammer U2, Walter M2, Knüpfer S C2, Schneider M P2, Seifert B3, Mehnert U2, Kessler T M2 1. Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital and Department of Urology, University Hospital Basel, 2. Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, 3. Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics, University of Zürich

PD06-11 REPRODUCIBILITY OF SUPRASPINAL RESPONSES TO AUTOMATED, REPETITIVE BLADDER FILLING - AN FMRI STUDY

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<0.001 using the false discovery rate (FDR) correction to adjust for multiple comparisons. Differences between both visits were investigated using a paired t test. In addition, regions of interest (ROI) were defined using the Wake Forrest University Pickatlas and included as a mask in order to restrict the voxel-by-voxel statistical analysis (familywise error (FWE)-correction) to pre-specified brain areas. RESULTS: Within-group WB analysis revealed activation in the following brain areas for visit 1: bilateral prefrontal gyrus (PFG); anterior cingulate cortex (ACC), mid and posterior cingulate cortex; left insula; hippocampus; temporal and parietal gyrus; and for visit 2: bilateral PFG; ACC; bilateral insula; bilateral basal ganglia. No statistical differences in BOLD signal changes were detected between both visits. ROI analyses, a more sensitive approach, detected reproducibility of BOLD signal changes in the following areas: PFG, ACC and insula. CONCLUSIONS: This study confirms that automated, repetitive bladder filling of body warm saline using a MR-compatible and MRsynchronized infusion-drainage system shows reproducible BOLD signal changes in specific areas, known from previous neuroimaging studies to be involved in supraspinal lower urinary tract control.

MP17-14 MORE THAN 15 YEARS EXPERIENCE WITH INTRADETRUSOR ONABOTULINUMTOXINA INJECTIONS FOR TREATING REFRACTORY NEUROGENIC DETRUSOR OVERACTIVITY: LESSONS TO BE LEARNED

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[11_TD