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

BMC Urology, Nov 2016

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.

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

Lely et al. BMC Urology Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort Stéphanie van der Lely 0 3 Martina Stefanovic 0 3 Melanie R. Schmidhalter 0 3 Marta Pittavino 2 Reinhard Furrer 2 Martina D. Liechti 0 3 Martin Schubert 1 Thomas M. Kessler 0 3 Ulrich Mehnert 0 3 0 Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital , Forchstrasse 340, 8008 Zürich , Switzerland 1 Neurophysiology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital , Forchstrasse 340, 8008 Zürich , Switzerland 2 Institute of Mathematics, University of Zürich , Winterthurerstrasse 190, 8057 Zürich , Switzerland 3 Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital , Forchstrasse 340, 8008 Zürich , Switzerland 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. Sensory evoked potential; Electroencephalography; Lower urinary tract; Urinary bladder; Urethra; Randomized; Lower urinary tract dysfunction; Current perception threshold; A-delta afferent fibers; Electrical stimulation - Background Lower urinary tract symptoms (LUTS) such as urinary urgency, frequency and incontinence, imply a massive impairment of quality of life [1, 2]. LUTS are highly prevalent and a large proportion of LUTS are found to be associated with afferent nerve dysfunction [1, 3–5]. Assessment of afferent pathways in patients with LUTS is however a challenge. Specific diagnostic tools for an objective and reproducible measurement of bladder and urethral afferent nerve function are missing. Yet, filling cystometry (FC) is the standard method used in clinical practice for the assessment of bladder sensations [6–10]. Nevertheless, FC largely depends on the subjective perceptions and collaboration of the patient and is hence not an objective measurement of bladder sensations. In addition, the reliability of the FC is questionable and its variability and outcome resolution is too large to detect differences smaller than 100 mL [11, 12]. Moreover, FC only covers sensory information from the bladder but not from the urethra. Current perception threshold (CPT) testing is another method of assessing sensations from the lower urinary tract (LUT). CPT testing is performed by asking the subject to indicate the onset of sensation when an increasing electrical stimulus is applied [13]. It was shown that this method is safe and well tolerated by healthy (...truncated)


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Stéphanie van der Lely, Martina Stefanovic, Melanie Schmidhalter, Marta Pittavino, Reinhard Furrer, Martina Liechti, Martin Schubert, Thomas Kessler, Ulrich Mehnert. Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort, BMC Urology, 2016, pp. 69, 16, DOI: 10.1186/s12894-016-0188-9