Urinary Bladder, Overactive Clinical Trial
Official title:
Study of Brain Areas Involved in the Sensation of Bladder Filling in Healthy Females and Untreated Females With Overactive Bladder (OAB) Using fMRI and Water Pressure Urodynamics
Overactive Bladder syndrome (OAB) is a medical condition with symptoms of urgency, with or without incontinence, usually with frequency and nocturia, with no proven infection or obvious pathology 1. This study will explore the relationship between OAB, obstruction and the micro contractions as well as the brain areas involved in both normal desire to void and urgency, gaining a better understanding of the bladder pathophysiology and in the future allowing better strategy of treatment options for patients suffering from OAB.
Overactive Bladder Syndrome The International Continence Society (ICS) has defined
Overactive Bladder syndrome (OAB) as a medical condition with symptoms of urgency, with or
without incontinence, usually with frequency and nocturia, with no proven infection of
obvious pathology.
OAB has an overall prevalence in Western Europe and the United States of 16% to 17%.
Epidemiological evidence indicates that symptoms of OAB are common and likely to affect up
to 50-100 million persons worldwide. In the EPIC study which was conducted in 5 countries in
> 19000 men and women aged > 18 years, using the ICS definitions for OAB, the prevalence of
OAB was 10.8% in men and 12.8% in women, and its prevalence increased with age. The
prevalence in women for storage was 59.2%, in voiding 19.5% and in post micturition symptoms
14.2%.
The fundamental symptom is urgency, which is widely considered to be the driver of other
urological symptoms. Urgency is a sudden compelling desire to pass urine, which is difficult
to defer. The urological symptoms can have a considerable negative impact on quality of
life, typically resulting in embarrassment and loss of dignity, which might affect
relationships, intimacy and self-image.
Conventional urodynamic test Diagnostic testing of lower urinary tract function by
performing urodynamic investigations is currently widely accepted. The aim of the clinical
urodynamics is to produce symptoms whilst making precise measurements in order to identify
underlying causes for the symptoms and to quantify the related pathophysiological processes.
Urodynamics allows direct assessment of lower urinary tract function by the measurement of
physiological parameters (e.g. voiding pressure parameters; minimal urethral opening
detrusor pressure and urethral resistance factor), micturitions volume and leakage volume).
Urodynamics cannot be performed as an automated protocol due to current limitations of
urodynamic equipment and the lack of consensus on the precise method of measurement, signal
processing, quantification, documentation and interpretation. The Good Urodynamic Practices
developed by ICS provides guidelines regarding the strategy for urodynamic measurement,
equipment set up and configuration, signal testing, plausibility controls, pattern
recognition, and artefact correction.
During cystometry, involuntary detrusor contractions can only be found in 40% to 60% of
patients with OAB symptoms. Detrusor overactivity contractions can occur either during
filling or at the end. Conventional urodynamic remains the gold standard for investigating
lower urinary tract dysfunction.
Functional Magnetic Resonance Imaging fMRI is an imaging modality that has recently been
further developed to study the different parts of the human body through blood flow changes.
In close collaboration with Maastricht University, Scannexus has made multiple 7 Tesla MRI
scans available for our study in order to gain further insight into brain functioning areas.
Bladder Sensations Most of the understanding on the experience of bladder sensation during
filling in normal individuals is based upon the work of Wyndaele and De Wachter. The
sensation scoring system developed seek to determine the underlying reasons an individual
patient usually void and is not meant to serve as an index of urgency or severity. The
4-point scoring scale ranges from voiding out of convenience (no urgency=0) to desperate
urgency score=3) to capture perception of urgency on a continuum rather per se. The
condition is recognised clinically as the 'Overactive Bladder (OAB) Symptom Complex'. It is
associated with increased sensations to void which result in an increased voiding frequency,
as determined from voiding diaries. OAB is further characterised during cystometric
investigation by the occurrence of involuntary contractions of the bladder during the
filling phase and, typically in the 'full bladder' by a strong sensation described as
'urgency' (a strong compelling desire to void that cannot be deferred which is more intense
than a normal urge to void).
Overactive bladder syndrome (OAB) is associated with episodic increased bladder sensations
to void, which result in increased in voiding frequency. During cystometric investigations,
OAB is also characterised by the occurrence of involuntary bladder contractions during the
filling phase and typically in the full bladder, a strong sensation described as urgency
(described as a strong compelling desire to void that cannot be deferred and is more intense
than the normal urge to void). It is during these urgency episodes that leakages (urgency
incontinence) sometimes occur. In 46% of patients with the sensation of urgency, it is
associated with bladder contractions.
Many studies investigated the link between patient reported sensations and bladder
properties using standard rapid fill cystometry. This leads to the concept that bladder
sensation is episodic. These episodic sensations are supposedly greater in patients with OAB
and occur in lower bladder volumes, thus generating the sensation of urgency and more
frequent voiding.
As described in literature sensations associated with bladder filling were different from
those of imminent voiding. The sensations during filling were associated with a generalised
feeling in the lower abdomen while the more intense sensations of imminent pre-void were
located deeper down in the urethra. This anatomical variation may reflect different
sensations and different underlying mechanisms. This supports that there are two systems
generating sensation: 'continuous sensation' associated with the early filling phase and
intense phasic sensations associated with the urethra.
An alternative view of bladder sensation was formulated many years ago. It proposes that the
information from the bladder is generated continuously and that an awareness of bladder
volumes is available through the entire filling phase. This is supported by
neuro-physiological data demonstrating an almost continuous afferent outflow from the
bladder receptors as the bladder fills. As a conclusion the physiological bases of the
sensation or "urge" or "urgency" is still unknown.
Moreover, patients with OAB with or without detrusor overactivity (DO) on urodynamics all
have in common that they have a sense of urgency. This sense is described as a sudden,
compelling desire to void, which cannot be postponed. Affected individuals have the fear to
loose urine (incontinence) and some even actually do. It is still not known if the same
brain areas are involved in a normal desire to void in controls, as in OAB patients both
with and without DO when they feel urgency. In our study we would like to answer this
question by conducting simple urodynamics during an fMRI scan while the patient's bladder is
filled through normal diuresis and their sense of urgency is registered through a push
button.
In the past a few studies have been conducted with the fMRI of the central nervouse system
in relation to bladder control. Poor bladder control has been reported to be specifically
associated with inadequate activation of orbitofrontal cortex. Clinically, frontal cortical
lesions are known to cause bladder control problems.. In addition, urinary urgency in
patients with OAB was shown to be associated with increased activation of the limbic cortex
through fMRI studies in women with OAB. A more recent study with fMRI showed that there were
significant and vast changes in the brain's functional connectivity when bladder is filled,
suggesting that the central process responsible for the increased control during the full
bladder state appears to largely rely on the how distributed brain systems. In all these
studies, a 3 Tesla fMRI has been used. The 7 Tesla fMRI which is intended to be used in our
study will enable us to study brain areas that are more difficult to assess with 1,5 and 3
Tesla.
Moreover, none of the previous studies have included a protocol to measure bladder pressure,
bladder sensation and fMRI scans of the brain simultaneously.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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