title: Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov; Identifier: NCT02272309 .
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: van der Lely
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Stefanovic
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Schmidhalter
authors.affiliation: Institute of Mathematics, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Pittavino
authors.affiliation: Institute of Mathematics, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Furrer
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Martina D
authors.initials: MD
authors.lastname: Liechti
authors.affiliation: Neurophysiology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kessler
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital, Forchstrasse 340, 8008, Zürich, Switzerland. ulrich.mehnert@balgrist.ch.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mehnert
mesh_terms: D002985:Clinical Protocols; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012016:Reference Values; D012107:Research Design; D014521:Urethra / Q000294:innervation / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*
keywords: A-delta afferent fibers; Current perception threshold; Electrical stimulation; Electroencephalography; Lower urinary tract; Lower urinary tract dysfunction; Randomized; Sensory evoked potential; Urethra; Urinary bladder