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

Multiple Sclerosis, Neurogenic Lower Urinary Tract Dysfunction, Overactive Bladder, Spinal Cord Injury

lower urinary tract, bladder, supraspinal control, neuroimaging, functional magnetic resonance imaging, diffusion tensor imaging, functional connectivity, neurogenic lower urinary tract dysfunction, overactive bladder, multiple sclerosis, spinal cord injury

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.

Switzerland