Altered brain processing of rectal sensation in children with functional fecal incontinence.

Fecal incontinence, unintentional passage of stool, is a common condition in
children, with a prevalence of 3% in a Dutch population-based study. It is a
source of distress and concern for children and their families. Functional
fecal incontinence can be subdivided in constipation-associated fecal
incontinence as described by the ROME III criteria as functional constipation
(FC) and functional non-retentive fecal incontinence (FNRFI). A subgroup of
children with FC and FNRFI remains symptomatic up to adolescence or young
adulthood. A clear relation between treatment failure and ano-rectal parameters
has never been identified. Understanding the underlying physical abnormalities
of these continence disorders is crucial for the development of better
treatment strategies.
Children with functional fecal incontinence (both FC and FNRFI) often report
*loss of defecatory urge sensation*. Therefore diminished rectal sensation was
suggested a contributing factor. However, when examining rectal sensation with
pressure-controlled rectal distension no abnormal afferent sensation could be
identified in children with FC and FNRFI. Furthermore, the involuntary internal
anal sphincter relaxes sufficiently when rectal distension occurs in children
with FC and FNRFI. However, the role of the voluntary external anal sphincter
in the pathogenesis of fecal incontinence in these patients, is uncertain.
Clearly, continence depends also on cerebral control of the external sphincter
and pelvic floor muscles. We propose that this cerebral control is impaired,
with altered or diminished brain processing of rectal urge sensation.
Increasing studies have been conducted to unravel the brain processing of
visceral sensation in adults with functional gastrointestinal disorders using
functional magnetic resonance imaging (fMRI). fMRI studies in adults showed
that the anterior cingulated cortex, insular cortex, thalamus and primary
somatosensory cortex are activated during rectal sensory stimuli. fMRI in
combination with rectal distension has never been performed in the pediatric
population.

Our hypothesis is that the brain processing of rectal sensation is impaired in
children with functional fecal incontinence, leading to reduced cerebral
activity during rectal distension.
We will perform a pilot study using fMRI in combination with rectal barostat to
measure regional cerebral activity in response to rectal distension to
determine (1) if fMRI can detect cerebral activity in children with functional
fecal incontinence during sensation of urge to defecate; and (2) if differences
in cerebral activity exist between FC and FNRFI patients.

In this observational pilot-study, functionale MRI testing will be performed
simultaneously with rectal barostat.

Baseline measures
At intake, a standardized interview will be conducted to determine demographic
data, defecation pattern and defecation related behavior. Abdominal and rectal
examination will be performed to evaluate the presence of fecal mass in the
rectumm this is part of standard medical care.
Colonic transit time will be measured. This will be performed as previously
prescribed and is considered a standard diagnostisc procedure to differentiate
between FC and FNRFI. After discontinuation of oral and rectal laxatives, 1
capsule with 10 radio-opaque markers will be ingested on 6 consecutive days. On
day 7, a single abdominal radiograph will be obtained and the number of markers
will be counted in the right, left and rectosigmoid colonic regions based on
identification of bony landmarks and gaseous outlines.

Rectal barostat
A rectal barostat test will be performed as previously reported. A
non-compliant polyethylene balloon with a maximum volume of 500 ml is connected
to a computer-driven barostat device. The balloon is fixed on a 8 meter long
silicone catheter thereby the barostat device can be located in a different
area than the MRI scanner. The lubricated balloon will be introduced manually
into the rectum.
Prior to the pressure-controlled distension protocol, the balloon is unfolded
by volume increase until a volume of 150 ml was reached. The inflated balloon
is then pulled back against the pelvic floor. After deflation, the minimal
distension pressure (MDP) will be determined by stepwise increasing the
intra-balloon pressure (1 mmHg steps of 1 minute).
A 5 minute period with a deflated balloon is followed to allow for rectal
adaptation. An intermittent distension protocol with step-wise increases of 3
mmHg to 24 mmHg above MDP (i.e. 6 mmHg above the 95th percentile of urge to
defecate in FC) will be used to determine rectal sensation. Each step lasts 60
seconds with intervals of 60 seconds at MDP. At 30 seconds rectal sensation
will be scored for each step. An ordinal scale from 0-5 is used to score
sensation: 0=no sensation, 1=first sensation, 2=urge to defecate, 3=moderate
urge to defecate, 4=severe urge to defecate, 5=pain.

MRI scanning
After the distension protocol the subject will be positioned in the MRI
scanner. Functional scanning will be performed by a 3.0 T Intera fMRI scanner
(Philips Medical Systems) using blood oxygenlevel dependent (BOLD) contrast.
In addition, to obtain anatomical information for each subject, high resolution
anatomical scans will be performed for co-registration of the fMRI data.
The rectal pressure at which urge to defecate is felt during the first
distension protocol will be used during two scanning sessions of 5 stimulations
consisting of repetitions of 30 seconds of rectal stimulation followed by 30
seconds of rest with MDP. Between the two sessions there will be 5 minute
resting time without scanning.

There are no risks related to rectal barostat and fMRI research.
The burden of the rectal barostat is considered minimal. The introduction of
the rectal catheter can be uncomfortable, therefore an extensive preparation of
the patient will take place. Rectal distension can cause abdominal pain or
cramps. However the pressure on the rectum will be lower compared to thresholds
of abdominal pain in earlier studied children, therefore in current study
chances are low that abdominal pain occurs. If a child experiences abdominal
pain the study will be ended.
MR imaging is a non-invasive modality. All patients will receive extensive
information about the MRI procedures beforehand. Extensive coaching and
preparation of the children and adolescents to prevent stress and anxiety will
be part of the standard procedures: the adolescents get the opportunity to get
acquainted with the MRI scanner and its procedures before the real scan session
starts, in order to prevent stress and anxiety. There will be minor discomfort
caused by having to lie absolutely still for several minutes and being fixed in
a small space. Therefore a rest period is added to the protocol and subjects
suffering from claustrophobia are excluded from participation. Considering the
coaching and preparation of the adolescent patients beforehand, we consider the
burden of this procedure to be minimal. Since MR imaging is considered a safe
standard medical procedure, also in children and adolescents, we evaluate the
risks associated with MR scanning to be negligible.