Supraspinal Control of Lower Urinary Tract Function in Healthy Controls and Patients With Bladder Dysfunction

The purpose of this study is to provide profound insight into the supraspinal neuronal mechanisms and networks responsible for lower urinary tract (LUT) control and to verify, amend or adjust neuronal circuitry models established from findings in healthy subjects in the context of neurogenic and non-neurogenic LUT dysfunction.

The subject recruitment will be performed within the Neuro-Urology outpatient clinic at the Balgrist University Hospital and in collaboration with the Departments of Neurology, Urology and Gynecology at the University Hospital Zürich.

The following subject groups will be recruited: 1) healthy controls (n=22), Non-neurogenic overactive bladder (NNOAB) patients (n=20), multiple sclerosis (MS) patients with OAB (n=15), MS patients without OAB (n=15), spinal cord injury (SCI) patients with neurogenic detrusor overactivity (n=24).

After inclusion, all subjects and patients will undergo one to two functional magnetic resonance imaging (fMRI) sessions. NNOAB patients might undergo an additional fMRI session after receiving overactive bladder (OAB) treatment (such as antimuscarinics, intradetrusor injections of botulinum toxin type A). Spinal cord injury (SCI) patients with neurogenic detrusor overactivity will undergo an additional fMRI session 5-7 weeks after intradetrusor injections of botulinum toxin type A.

High-resolution anatomical images and functional blood-oxygen-level-dependent (BOLD)-signal sensitive images will be acquired. In addition to the fMRI, diffusion tensor imaging (DTI) sequences will be recorded after the anatomical scans to provide information about the structural supraspinal connectivity.

Study endpoints are changes of the BOLD signal in regard to location and intensity, structural and functional connectivity (FC) between previously described supraspinal centers involved in LUT control, and statistical differences of changes in BOLD signals, structural and functional connectivity between patients and healthy controls.

All acquired fMRI data will be transferred to an off-line workstation running BrainVoyager QX or Statistical Parametric Mapping (SPM) Version 8. The functional data will be pre-processed for motion correction, spatial smoothing, linear trend removal, and temporal high-pass filtering. With both programs statistical analysis and graphical presentation of the results can be performed.

The DTI records will be evaluated with SPM8, BrainVoyager QX or other programs like Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) and DTI-Studio. To estimate FC we will use SPM8 or the brain connectivity toolbox. Both softwares allow the estimation of rest- and task-related connectivity on single subject and group level with corrected statistical threshold.

Overall, 96 subjects for the main study are estimated to be sufficient to demonstrate significant differences between groups.

Eligibility Criteria:
Inclusion Criteria:

Healthy controls

* Right handed
* MR suitability
* Written informed consent
* unimpaired LUT function

MS patients with OAB

* Right handed
* MR suitability
* Written informed consent
* diagnosis of MS according to the McDonald criteria
* Expanded Disability Status Scale (EDSS) ≤ 6
* OAB symptoms since \> 6 months

  * ≥ 3 episodes of urinary urgency
  * frequency \> 8/24h
* with or without detrusor overactivity

MS patients without OAB

* Right handed
* MR suitability
* Written informed consent
* diagnosis of MS according to the McDonald criteria
* Expanded Disability Status Scale (EDSS) ≤ 6

Patients with NNOAB

* Right handed
* MR suitability
* Written informed consent
* idiopathic OAB symptoms since \> 6 months

  * ≥ 3 episodes of urinary urgency
  * frequency \> 8/24h
* refractory to antimuscarinic treatment for ≥ 1 month
* indication for intradetrusor injections of Botulinumtoxin Type A
* willingness and ability to perform self-catheterization

SCI patients with neurogenic detrusor overactivity

* Right handed
* MR suitability
* Written informed consent
* neurogenic detrusor overactivity due to SCI
* indication for intradetrusor injections of botulinum toxin type A

Exclusion Criteria:

Healthy controls

* impaired LUT function
* pregnancy or breast feeding
* no informed consent
* any craniocerebral injury or surgery
* any permanent ferromagnetic implant
* any previous surgery of the LUT or genitalia
* any anatomical anomaly of the LUT or genitalia
* any LUT malignancy
* postvoid residual urine volume (PVR) \> 150ml
* current urinary tract infection
* any LUT symptoms

  * ≥ 3 episodes of urinary urgency
  * frequency \> 8/24h

MS patients with OAB

* pregnancy or breast feeding
* any permanent ferromagnetic implant
* any neurological or psychological disease despite MS
* any craniocerebral injury or surgery
* any previous surgery of the LUT or genitalia
* any anatomical anomaly or malignancy of the LUT or genitalia
* any metabolic disease
* PVR \> 150ml
* any concomitant treatment for the LUT (e.g. neuromodulation)
* Stress urinary incontinence
* any condition other than MS that might explain OAB symptoms
* current urinary tract infection
* indwelling catheters or the necessity to perform self-catheterization

MS patients without OAB

* pregnancy or breast feeding
* any permanent ferromagnetic implant
* any neurological or psychological disease despite MS
* any craniocerebral injury or surgery
* any previous surgery of the LUT or genitalia
* any anatomical anomaly or malignancy of the LUT or genitalia
* any metabolic disease
* PVR \> 150ml
* any concomitant treatment for the LUT (e.g. neuromodulation)
* Stress urinary incontinence
* any LUT symptoms

  * ≥ 3 episodes of urinary urgency
  * frequency \> 8/24h
* indwelling catheters or the necessity to perform self-catheterization
* detrusor overactivity
* current urinary tract infection

Patients with NNOAB

* pregnancy or planned within next 8 months, breast feeding
* any permanent ferromagnetic implant
* any neurological, psychological, metabolic or cardiovascular disease
* any craniocerebral injury or surgery
* any previous surgery of the LUT or genitalia within the last year or that is related to the OAB symptoms
* any anatomical anomaly or malignancy of the LUT or genitalia
* PVR \> 150ml
* Stress urinary incontinence
* indwelling catheters or the necessity to perform self-catheterization
* any concomitant treatment for the LUT (e.g. neuromodulation)
* current urinary tract infection

SCI patients with neurogenic detrusor overactivity

* pregnancy or breast feeding
* any permanent ferromagnetic implant
* any neurological or psychological disease despite SCI
* any craniocerebral injury or surgery
* any previous surgery of LUT of genitalia
* any anatomical anomaly or malignancy of the LUT or genitalia
* any metabolic disease
* any concomitant treatment for the LUT (e.g. neuromodulation)
* current urinary tract infection