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| Name | Class |
|---|---|
| Swiss National Science Foundation | OTHER |
| Balgrist University Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy controls | Experimental | Procedure: 1-2 fMRI measurements within 4 weeks from first exam. Measurements include repetitive retrograde bladder filling via transurethral catheter at different bladder volumes and temperatures (e.g. bladder cooling, body warm or room temperature)of the filling liquid. |
|
| MS with OAB | Experimental | Procedure: 1-2 fMRI measurements within 4 weeks from first exam. Measurements include repetitive retrograde bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid. |
|
| MS without OAB | Experimental | Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid. |
|
| NNOAB | Experimental | Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid plus additional post-treatment fMRI scan 5 to 7 weeks after OAB treatment (such as antimuscarinics, intradetrusor injections of botulinum toxin type A) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fMRI | Other | 2 measurements using functional magnetic resonance imaging in a 3T scanner |
|
| Measure | Description | Time Frame |
|---|---|---|
| Bold signal | During fMRI measurements the changes of BOLD signal intensity in respect to certain supraspinal areas (e.g. pons, insula, anterior cingulate cortex, thalamus, supplementary motor area, prefrontal cortex) will be evaluated. Variables are age, bladder volume, urgency and attention. | baseline and 4 weeks |
| Structural and functional connectivity | Acquired data from the above mentioned measurements will be used to analyze structural and functional connectivity between supraspinal areas involved in the LUT control, especially between prefrontal, thalamus, insula, and anterior cingulate cortex. Variables are age, bladder volume, urgency and attention. Correlations of neuronal activity from the fMRI-data will be estimated using SPM8, brain connectivity tool box. | baseline and after potential OAB treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Side effects | Pain, Lower urinary tract infection | 3 years |
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Inclusion Criteria:
Healthy controls
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
with or without detrusor overactivity
MS patients without OAB
Patients with NNOAB
Right handed
MR suitability
Written informed consent
idiopathic OAB symptoms since > 6 months
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
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
MS patients with OAB
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
indwelling catheters or the necessity to perform self-catheterization
detrusor overactivity
current urinary tract infection
Patients with NNOAB
SCI patients with neurogenic detrusor overactivity
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| Name | Affiliation | Role |
|---|---|---|
| Ulrich Mehnert, MD | Neuro-Urology, Spinal Cord Injury Center & Research, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland | Principal Investigator |
| Thomas M Kessler, MD | Neuro-Urology, Spinal Cord Injury Center & Research, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland | Principal Investigator |
| Spyros Kollias, MD | Institute of Neuroradiology, University Hospital Zurich, Sternwartstrasse 6, 8091 Zurich, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital | Zurich | 8008 | Switzerland | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24848086 | Result | Walter M, Michels L, Kollias S, van Kerrebroeck PE, Kessler TM, Mehnert U. Protocol for a prospective neuroimaging study investigating the supraspinal control of lower urinary tract function in healthy controls and patients with non-neurogenic lower urinary tract symptoms. BMJ Open. 2014 May 21;4(5):e004357. doi: 10.1136/bmjopen-2013-004357. | |
| 25132340 |
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| SCI with neurogenic detrusor overactivity | Experimental | Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid plus 1 additional post-treatment fMRI scan 5 to 7 weeks after intradetrusor injections of botulinum toxin type A |
|
| bladder filling | Other | Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements. |
|
| bladder cooling | Other | Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements. |
|
| additional post-treatment fMRI scan | Other | Should NNOAB or SCI patients receive a study independent OAB therapy by their treating physician after the 2nd fMRI scan, they will be invited for an additional third fMRI scan. |
|
| University Hospital Zürich |
| Zurich |
| 8008 |
| Switzerland |
| Leitner L, Walter M, Freund P, Mehnert U, Michels L, Kollias S, Kessler TM. Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity. BMC Urol. 2014 Aug 18;14:68. doi: 10.1186/1471-2490-14-68. |
| 27617867 | Result | Leitner L, Walter M, Jarrahi B, Wanek J, Diefenbacher J, Michels L, Liechti MD, Kollias SS, Kessler TM, Mehnert U. A novel infusion-drainage device to assess lower urinary tract function in neuro-imaging. BJU Int. 2017 Feb;119(2):305-316. doi: 10.1111/bju.13655. Epub 2016 Oct 20. |
| 30776530 | Result | Walter M, Leitner L, Michels L, Liechti MD, Freund P, Kessler TM, Kollias S, Mehnert U. Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants - A fMRI study. Neuroimage. 2019 May 1;191:481-492. doi: 10.1016/j.neuroimage.2019.02.031. Epub 2019 Feb 15. |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D053201 | Urinary Bladder, Overactive |
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D059411 | Lower Urinary Tract Symptoms |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
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