Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Urology
Published in: BMC Urology 1/2016

Open Access 01-12-2016 | Study protocol

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

Authors: Stéphanie van der Lely, Martina Stefanovic, Melanie R. Schmidhalter, Marta Pittavino, Reinhard Furrer, Martina D. Liechti, Martin Schubert, Thomas M. Kessler, Ulrich Mehnert

Published in: BMC Urology | Issue 1/2016

Login to get access

Abstract

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.
Literature
1.
Coyne KS, Wein AJ, Tubaro A, Sexton CC, Thompson CL, Kopp ZS, Aiyer LP. The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS. BJU Int. 2009;103 Suppl 3:4–11.CrossRefPubMed
2.
Irwin DE, Milsom I, Kopp Z, Abrams P, Cardozo L. Impact of overactive bladder symptoms on employment, social interactions and emotional well-being in six European countries. BJU Int. 2006;97(1):96–100.CrossRefPubMed
3.
Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011;108(7):1132–8.CrossRefPubMed
4.
Yoshimura N. Lower urinary tract symptoms (LUTS) and bladder afferent activity. Neurourol Urodyn. 2007;26(6 Suppl):908–13.CrossRefPubMed
5.
Fowler CJ. Bladder afferents and their role in the overactive bladder. Urology. 2002;59(5 Suppl 1):37–42.CrossRefPubMed
6.
Schafer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, Sterling AM, Zinner NR, van Kerrebroeck P, International Continence S. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn. 2002;21(3):261–74.CrossRefPubMed
7.
Heeringa R, van Koeveringe GA, Winkens B, van Kerrebroeck PE, de Wachter SG. Degree of urge, perception of bladder fullness and bladder volume--how are they related? J Urol. 2011;186(4):1352–7.CrossRefPubMed
8.
Erdem E, Akbay E, Doruk E, Cayan S, Acar D, Ulusoy E. How reliable are bladder perceptions during cystometry? Neurourol Urodyn. 2004;23(4):306–9.
9.
De Wachter S, Van Meel TD, Wnydaele JJ. Can a faked cystometry deceive patients in their perception of filling sensations? A study on the reliability of spontaneously reported cystometric filling sensations in patients with non-neurogenic lower urinary tract dysfunction. Neurourol Urodyn. 2008;27(5):395–8.CrossRefPubMed
10.
Groen J, Pannek J, Castro Diaz D, Del Popolo G, Gross T, Hamid R, Karsenty G, Kessler TM, Schneider M, t Hoen L, et al. Summary of European Association of Urology (EAU) guidelines on Neuro-Urology. Eur Urol. 2016;69(2):324–33.CrossRefPubMed
11.
Virseda M, Salinas J, Esteban M, Mendez S. Reliability of ambulatory urodynamics in patients with spinal cord injuries. Neurourol Urodyn. 2013;32(4):387–92.CrossRefPubMed
12.
Bellucci CH, Wollner J, Gregorini F, Birnbock D, Kozomara M, Mehnert U, Kessler TM. Neurogenic lower urinary tract dysfunction--do we need same session repeat urodynamic investigations? J Urol. 2012;187(4):1318–23.CrossRefPubMed
13.
14.
De Wachter S, Wyndaele JJ. Quest for standardisation of electrical sensory testing in the lower urinary tract: the influence of technique related factors on bladder electrical thresholds. Neurourol Urodyn. 2003;22(2):118–22.CrossRefPubMed
15.
De Laet K, De Wachter S, Wyndaele JJ. Current perception thresholds in the lower urinary tract: Sine- and square-wave currents studied in young healthy volunteers. Neurourol Urodyn. 2005;24(3):261–6.CrossRefPubMed
16.
Ulrich Mehnert, André Reitz, Maya Ziegler, Peter A. Knapp, Brigitte Schurch. Does Tolterodine Extended Release Affect the Bladder Electrical Perception Threshold? A Placebo Controlled, Double-Blind Study With 4 and 8 mg in Healthy Volunteers. The Journal of Urology. 2007;178(6):2495-2500.
17.
Ukimura O, Ushijima S, Honjo H, Iwata T, Suzuki K, Hirahara N, Okihara K, Mizutani Y, Kawauchi A, Miki T. Neuroselective current perception threshold evaluation of bladder mucosal sensory function. Eur Urol. 2004;45(1):70–6.CrossRefPubMed
18.
Knupfer SC, Liechti MD, Gregorini F, De Wachter S, Kessler TM, Mehnert U. Sensory function assessment of the human male lower urinary tract using current perception thresholds. Neurourol Urodyn. 2016 [Epub ahead of print].
19.
Cruccu G, Aminoff MJ, Curio G, Guerit JM, Kakigi R, Mauguiere F, Rossini PM, Treede RD, Garcia-Larrea L. Recommendations for the clinical use of somatosensory-evoked potentials. Clin Neurophysiol. 2008;119(8):1705–19.CrossRefPubMed
20.
Deltenre PF, Thiry AJ. Urinary bladder cortical evoked potentials in man: suitable stimulation techniques. Br J Urol. 1989;64(4):381–4.CrossRefPubMed
21.
Chiappa KH, Ropper AH. Evoked potentials in clinical medicine (first of two parts). N Engl J Med. 1982;306(19):1140–50.CrossRefPubMed
22.
Ganzer H, Madersbacher H, Rumpl E. Cortical evoked potentials by stimulation of the vesicourethral junction: clinical value and neurophysiological considerations. J Urol. 1991;146(1):118–23.PubMed
23.
Hansen MV, Ertekin C, Larsson LE. Cerebral evoked potentials after stimulation of the posterior urethra in man. Electroencephalogr Clin Neurophysiol. 1990;77(1):52–8.CrossRefPubMed
24.
Sarica Y, Karacan I, Thornby JI, Hirshkowitz M. Cerebral responses evoked by stimulation of vesico-urethral junction in man: methodological evaluation of monopolar stimulation. Electroencephalogr Clin Neurophysiol. 1986;65(2):130–5.CrossRefPubMed
25.
Gregorini F, Wollner J, Schubert M, Curt A, Kessler TM, Mehnert U. Sensory evoked potentials of the human lower urinary tract. J Urol. 2013;189(6):2179–85.CrossRefPubMed
26.
Flavia Gregorini, Stephanie C. Knüpfer, Martina D. Liechti, Martin Schubert, Armin Curt, Thomas M. Kessler, Ulrich Mehnert. Sensory evoked potentials of the bladder and urethra in middle-aged women: the effect of age. BJU International. 2015;115:18-25.
27.
Sarica Y, Karatas M, Bozdemir H, Karacan I. Cerebral responses elicited by stimulation of the vesico-urethral junction (VUJ) in diabetics. Electroencephalogr Clin Neurophysiol. 1996;100(1):55–61.CrossRefPubMed
28.
Badr G, Carlsson CA, Fall M, Friberg S, Lindstrom L, Ohlsson B. Cortical evoked potentials following stimulation of the urinary bladder in man. Electroencephalogr Clin Neurophysiol. 1982;54(5):494–8.CrossRefPubMed
29.
Hansen MV, Ertekin C, Larsson LE, Pedersen K. A neurophysiological study of patients undergoing radical prostatectomy. Scand J Urol Nephrol. 1989;23(4):267–73.CrossRefPubMed
30.
Brookes ST, Donovan JL, Wright M, Jackson S, Abrams P. A scored form of the Bristol female lower urinary tract symptoms questionnaire: data from a randomized controlled trial of surgery for women with stress incontinence. Am J Obstet Gynecol. 2004;191(1):73–82.CrossRefPubMed
31.
Donovan JL, Peters TJ, Abrams P, Brookes ST, de aa Rosette JJ, Schafer W. Scoring the short form ICSmaleSF questionnaire. International Continence Society. J Urol. 2000;164(6):1948–55.CrossRefPubMed
32.
Costa P, Perrouin-Verbe B, Colvez A, Didier J, Marquis P, Marrel A, Amarenco G, Espirac B, Leriche A. Quality of life in spinal cord injury patients with urinary difficulties. Development and validation of qualiveen. Eur Urol. 2001;39(1):107–13.CrossRefPubMed
33.
Barry MJ, Fowler Jr FJ, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett AT. The American Urological Association symptom index for benign prostatic hyperplasia. The measurement committee of the American Urological Association. J Urol. 1992;148(5):1549–57. discussion 1564.PubMed
34.
Coyne KS, Thompson CL, Lai JS, Sexton CC. An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF. Neurourol Urodyn. 2015;34(3):255–63.CrossRefPubMed
35.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822–30.CrossRefPubMed
36.
Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D'Agostino Jr R. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000;26(2):191–208.CrossRefPubMed
37.
Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to assess the quality of life of urinary incontinent women. Br J Obstet Gynaecol. 1997;104(12):1374–9.CrossRefPubMed
38.
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.CrossRefPubMed
39.
Nasreddine ZS, Phillips N, Chertkow H. Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample. Neurology. 2012;78(10):765–6. author reply 766.CrossRefPubMed
40.
Silverman BW. Some aspects of the spline smoothing approach to non-parametric regression curve fitting. J R Stat Soc B Methodol. 1985;47(1):1–52.
41.
Abraham B, Ledolter J. Introduction To Regression Modeling. 2006.
42.
Davidson AC, Hinkley DV. Bootstrap Methods and Their Application. Cambridge University Press. 1997;48.
43.
Efron B. Bootstrap methods: another look at the jackknife. Annals of Statistics. 1979;7(1):1–26.CrossRef
44.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.CrossRefPubMed
45.
R Development Core Team. R. A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing;2015.
46.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4.CrossRef
47.
48.
49.
Metadata
Title
Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort
Authors
Stéphanie van der Lely
Martina Stefanovic
Melanie R. Schmidhalter
Marta Pittavino
Reinhard Furrer
Martina D. Liechti
Martin Schubert
Thomas M. Kessler
Ulrich Mehnert
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2016
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-016-0188-9

Other articles of this Issue 1/2016

BMC Urology 1/2016 Go to the issue

Research article

The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment with α1-adrenergic receptor blocker monotherapy: prospective analysis of elderly men

Research article

A novel stepwise micro-TESE approach in non obstructive azoospermia

Research article

Diagnostic and treatment factors associated with poor survival from prostate cancer are differentially distributed between regional and metropolitan Victoria, Australia

Research article

An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men

Research article

Increased risk for urological cancer associated with anxiety disorder: a retrospective cohort study

Research article

TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer