Lower urinary tract electrical sensory assessment: a systematic review and meta-analysis.

OBJECTIVES: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding. RESULTS: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.

Quantitative electrical pain threshold assessment in the lower urinary tract.

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.

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

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 (Pdetmax storage) of >40 cmH2 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 Pdetmax storage of >40 cmH2 O. Gender, underlying neurological disorder, and high Pdetmax 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.

Sensory function assessment of the human male lower urinary tract using current perception thresholds.

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 < 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). CONCLUSIONS: 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.

Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort.

BACKGROUND: 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. METHODS: This study is a prospective, randomized trial conducted at Balgrist University Hospital, Zürich, 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. DISCUSSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT02272309 .