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Student: Maxime van Meegdenburg
Student number: S1825097
Supervisor: Dr. P.M.A. Broens
Location: University Medical Centre Groningen
Department of Surgery
Different innervations for conscious and autonomic
external anal sphincter contraction:
analysis of fecal incontinent patients
2
SAMENVATTING
Achtergrond. Het is bekend dat de bewuste contractie van de dwarsgestreepte externe anale
sphincter wordt gecontroleerd door de nervus pudendus. Het is nog niet bekend of het deel
van de externe sphincter dat autonoom gecontraheerd wordt door de ano-externe sphincter
continentie reflex ook geïnnerveerd wordt door de nervus pudendus.
Methode. Retrospectief zijn de medische dossiers van 53 volwassen patiënten met pudendus
neuropathie en van zeventien volwassenen zonder pudendus neuropathie, die tussen 2010 en
2013 een uitgebreid anorectaal functie onderzoek hebben ondergaan, bekeken. De studie is
uitgevoerd in het Universitair Medisch Centrum Groningen in Nederland.
Resultaten. De patiënten met pudendus neuropathie waren significant ouder dan de patiënten
zonder pudendus neuropathie (mediaan: 41 versus 60 jaar, P = .013). De maximale sphincter
contractiliteit, oftewel de bewuste controle van de externe sphincter, was significant lager bij
patiënten met pudendus neuropathie, dan bij patiënten zonder pudendus neuropathie
(mediaan: 165 versus 235 mmHg, P = .007). Daarentegen, was de druk in het anale kanaal
tijdens de maximaal draaglijke of vast te houden sensatie, oftewel de onbewuste controle van
de externe sphincter, niet significant verschillend tussen de twee groepen (mediaan: 78 versus
118 mmHg). Verder bestond er geen relatie tussen de maximale sphincter contractiliteit en de
druk in het anale kanaal bij maximaal draaglijke of vast te houden sensatie. Meervoudige en
enkelvoudige lineaire regressie analyses lieten zien dat leeftijd en pudendus neuropathie
significant de maximale sphincter contractiliteit voorspelden, maar niet de druk in het anale
kanaal tijden maximaal draaglijke of vast te houden sensatie.
Conclusie. De autonome contractie van de externe sphincter wordt in ieder geval aangestuurd
door een ander deel van de nervus pudendus, dan de bewuste contractie. Waarschijnlijk wordt
de autonome contractie niet eens aangestuurd door de nervus pudendus. Het is nog niet
bekend welke zenuw wel verantwoordelijk is voor de autonome innervatie van de externe
sphincter. Een mogelijkheid is dat de autonome innervatie direct plaatsvindt via de vierde
sacrale zenuw.
3
SUMMARY
Background. The current understanding is that the conscious contraction of the striated
external anal sphincter is controlled by the pudendal nerve. It is not yet known whether the
part of the external sphincter that is autonomically contracted by the anal-external sphincter
continence reflex is also innervated by the pudendal nerve.
Methods. Retrospectively, we reviewed the medical records of fifty-three adult patients with
pudendal neuropathy and of seventeen adult patients without pudendal neuropathy who all
had undergone thorough anorectal function tests between 2010 and 2013. The study was
conducted at University Medical Center Groningen, the Netherlands.
Results. Patients in the pudendal neuropathy group were significantly older than patients in
the group without pudendal neuropathy (median: 41 versus 60 years, P = .013). Maximum
sphincter contractility, i.e., conscious control of the external sphincter, was significantly lower
in patients with pudendal neuropathy compared with patients without pudendal neuropathy
(median: 165 versus 235 mmHg, P = .007). In contrary, pressure in the anal canal at
maximum tolerable or retainable sensation, i.e., autonomic control of the external sphincter,
was not significantly different between the pudendal neuropathy group and the group without
pudendal neuropathy (median: 78 versus 118 mmHg). Additionally, the results showed that
there was no relation between maximum sphincter contractility and pressure in the anal canal
at maximum tolerable or retainable volume between the two groups. Multiple and simple
linear regression analyzes demonstrated that age and pudendal neuropathy significantly
predicted maximum sphincter contractility, but not pressure in the anal canal at maximum
tolerable or retainable sensation.
Conclusion. The autonomic contraction of the external sphincter is at least innervated by
another part of the pudendal nerve as the conscious contraction, presumably not even by the
pudendal nerve. It is not yet known which nerve is responsible for the autonomic contraction
of the external sphincter. Perhaps, it might be innervated directly by the fourth sacral nerve.
4
TABLE OF CONTENTS
Page
Samenvatting 2
Summary 3
1. Introduction 5
1.1. Anatomy pelvic floor and anorectum
1.2. Innervation pelvic floor and anorectum 7
1.3. Anal-external sphincter continence reflex 10
1.4. Problem definition 11
2. Material and methods 12
2.1. Patients
2.2. Constipation
2.3. Fecal incontinence 13
2.4. Measuring equipment
2.5. Anorectal function tests
2.6. Statistical analysis 15
3. Results 16
3.1. Patient characteristics
3.2. Results anorectal function tests
3.3. Linear regression analysis 19
4. Discussion 21
4.1. Discussion
4.2. Clinical relevance 22
4.3. Conclusion 23
5. Acknowledgements 24
6. References 25
5
1. INTRODUCTION
1.1 Anatomy pelvic floor and anorectum
Pelvic floor
The pelvic floor supports viscera of the pelvic cavity, helps maintain continence and plays a
role in the process of defecation. The pelvic floor consists of the levator ani, a thin striated
muscular sheet, with a central ligamentous structure that surrounds the rectum, the vagina,
and the urethra. The levator ani is comprised of three muscle parts: the pubococcygeus, the
iliococcygeus, and the puborectal muscle (Figure 1).(1) The puborectal muscle is an important
component for fecal continence. This striated muscle forms a U-shaped sling around the upper
anus that helps to pull the anus anteriorly and gives rise to the anorectal angle The anorectal
angle is held to be important in preserving fecal continence (Figure 2). Additionally,
contraction of the puborectal muscle increases anal canal pressure which helps maintain fecal
continence.(2,3) The puborectal muscle is continuous with the external anal sphincter.(4)
Figure 1. Superior view of pelvic floor muscles. The levator ani consists of the pubococcygeus, the
iliococcygeus, and the puborectal muscle. The puborectal muscle is an important component of the
levator ani for fecal continence.
6
Rectum and anal canal
The rectum is twelve to fifteen centimeters long and consists of a continuous layer of a
longitudinal muscle and an underlying circular smooth muscle.(5) Its main function is the
storage of faeces. The rectum can accommodate significant volumes of fecal mass with
minimum alteration in measured rectal pressure (i.e. rectal compliance). This phenomenon
occurs mainly at lower volumes of rectal filling as the rectum actively relaxes to
accommodate the fecal mass.(6) As the maximum tolerable volume is approached, even small
increases in volume are associated with changes in rectal pressure. Thus, reduction in rectal
capacity or compliance can lead to fecal incontinence. Furthermore, the ability to sense that
the rectum contains stool also plays a key role in fecal continence.
When the rectum passes the levator ani it continues as the anal canal, which varies
from two to five centimeters in length. The length of the anal canal is among other things
depending on gender and age.(5,7,8) The anal canal is encircled by the anal sphincter complex
that exists of the internal and external anal sphincter and the longitudinal muscle layer of the
rectum.(4)
Internal anal sphincter
The internal anal sphincter is a half a millimeter to five millimeter thick extension of the
circular smooth muscle layer of the rectum (Figure 3).(5,7) It is about three centimeters long
and terminates approximately ten millimeters above the skin of the anal verge.(2,9) The
internal anal sphincter consists mainly of slow-twitch muscle fibers that are fatigue
resistant.(10,11) The internal anal sphincter is responsible for 70% to 85% of the resting anal
pressure.(8,12-14) After sudden or constant distention of the rectum, however, it only
contributes 40% to 60% of the resting anal pressure. So, the internal anal sphincter is mainly
responsible for involuntary maintenance of fecal continence at rest.(12) Damage to the
internal anal sphincter can cause passive leakage of fecal contents and incontinence of
flatus.(1,15)
External anal sphincter
The internal anal sphincter is surrounded by the external anal sphincter, a one to ten
millimeter thick extension of the levator ani that extends down to the skin at the anal verge
(Figure 3).(5,7) Its main function is the voluntary contraction of the anal sphincter to prevent
Figure 2. The puborectal muscle during defecation and at rest. The puborectal muscle is
contracted at rest giving rise to the anorectal angle that is held to be important in preserving fecal
continence. During defecation the puborectal muscle relaxes leading to an increase in anorectal angle.
7
unwanted loss of stool. The conscious contraction of the external anal sphincter, however, is
only possible for a few minutes.(2) During these minutes the rectum can adapt to the filling of
the rectum with fecal mass, after which rectal pressure declines. The feeling of urgency abates
and defecation can be postponed. This explains why patients with external anal sphincter
injury often develop fecal urge incontinence. These patients have to rush to the toilet to make
it on time and prevent fecal incontinence.(15-17) The external anal sphincter can also be
contracted reflexly when intra-abdominal pressure suddenly increases, for example by
coughing.(18) Recently, it was demonstrated that the external anal sphincter can be contracted
autonomically by the anal-external sphincter continence reflex. This new continence reflex
will be explained later on.
1.2 Innervation pelvic floor and anorectum
The nervous system
The nervous system can be divided into the central nervous system and the peripheral nervous
system. The central nervous system contains the brain and the spinal cord. The peripheral
nervous system consists of cranial nerves and spinal nerves that connect the central nervous
system to the rest of the body.
The peripheral nervous system contains a motor (efferent) division and a sensory
(afferent) division. The sensory division conducts impulses from receptors to the central
nervous system and the motor division conducts impulses from the central nervous system to
muscles and glands.
The peripheral division can also be divided into a somatic nervous system and an
autonomic nervous system. The somatic nervous system is responsible for conscious or
voluntary motor activities. It conducts impulses from the central nervous system to skeletal
muscles and impulses from skeletal muscles, joints, and the skin to the central nervous
system. The autonomic or visceral nervous system is responsible for involuntary motor
activities. So, it conducts impulses from internal organs, and blood vessels to the central
nervous system and impulses from the central nervous system to smooth muscles, cardiac
muscles, and glands.
Figure 3. Representation of the anal canal and the sphincter complex.
8
Figure 4. Representation of the pudendal
nerve and his branches
At last, the autonomic nervous system is divided into the orthosympathetic part, the
parasympathetic part, and the enteric part. The orthosympathetic part mobilizes the body
during activity (i.e. flight or fight reactions), while the parasympathetic part is active during
rest and conserves energy. If the orthosympathetic part is active gastrointestinal motility is
reduced and if the parasympathicus is active the defecation process is stimulated. An
important part of the orthosympathetic nervous system is the sympathetic trunk that is formed
by ganglia and nerve fibers and extends the entire length of the vertebral column on each side.
At last, there is the enteric nervous system which is the intrinsic nervous system of the bowel.
Somatic innervation
The pudendal nerve arises from the sacral
plexus (S2 to S4) and gives off three
branches: the inferior rectal nerves, the
perineal nerves and the dorsal nerves of the
clitoris and the penis (Figure 4). The inferior
rectal nerves, that can also arise directly
from S2 to S4, are most important for the
defecation process and for fecal continence.
They supply motor innervation of the
external anal sphincter and sensory
innervation of the lower part of the anal
canal.(19) Pudendal neuropathy, therefore,
can lead to decreased sphincter contractility
resulting in fecal incontinence. There are
several causes of pudendal neuropathy, for
example: trauma to the pelvic area (during
childbirth), an operation in the pelvic area,
compression from lesions or tumors, and
causes for the development of peripheral
neuropathy (e.g. diabetes mellitus, multiple
sclerosis).
The levator ani is directly innervated
by nerve branches from the fourth sacral
nerve.(19)
Autonomic innervation
The orthosympathetic thoracic and lumbar pelvic splanchnic nerves originate from the tenth
thoracic through the second lumbar spinal cord segments. These thoracic and lumbar pelvic
splanchnic nerves come together in different plexuses, including the superior hypogastric
plexus. Meanwhile, some nerve branches pass the inferior mesenteric ganglion on their way
to the superior hypogastric plexus. The superior hypogastric plexus gives off the left and right
orthosympathetic hypogastric nerves that end in the inferior hypogastric plexuses. The
inferior hypogastric plexuses also receive orthosympathetic nerve fibers from sacral
splanchnic nerves that arise from the sacral part of the sympathetic trunk. At last, the inferior
hypogastric plexuses receive parasympathetic pelvic splanchnic nerve fibers originating from
S2 to S4. Thus, the inferior hypogastric plexuses are mixed plexuses that contain
orthosympathetic and parasympathetic nerve fibers. The inferior hypogastric plexuses supply
viscera of the pelvic cavity through several plexuses, namely: the rectal plexus, the vesical
plexus, the prostatic plexus, and the uterovaginal plexus (Figure 5).(19)
9
Fig
ure
5.
Au
ton
om
ic i
nn
erv
ati
on
rec
tum
an
d a
nal
can
al.
The
rect
um
is
suppli
ed b
y n
erv
es f
rom
the
infe
rio
r h
yp
og
astr
ic p
lexu
ses
that
rece
ive
sym
pat
het
ic n
erve
fib
ers
from
thora
cic,
lum
bar
, an
d s
acra
l pel
vic
spla
nch
nic
ner
ves
an
d p
aras
ym
pat
het
ic n
erve
fib
ers
from
pel
vic
spla
nch
nic
ner
ves
(S
2-S
4).
10
Figure 6. The classical fecal continence theory (A) and the
anal-external sphincter continence reflex (B). A, After a
person becomes aware of rectal filling sensations, the brain
orders the external anal sphincter to contract, preserving fecal
continence. B, The fecal mass activates continence receptors
in the anal canal leading to a spinal cord reflex that results in
contraction of the external anal sphincter without direct
influence from the brain.
1.3 Anal-external sphincter continence reflex
For a long time it was thought
that when a person becomes
aware of rectal filling sensations,
he can consciously contract the
external anal sphincter to prevent
the loss of fecal mass. Thus,
according to this understanding,
fecal continence depends on the
ability to feel rectal filling
sensations (Figure 6A).(20)
In a recent study the
existence of the anal-external
sphincter continence reflex was
demonstrated.(21) This new
theory suggests that fecal
continence is controlled by an
autonomic spinal cord reflex,
without direct influence from the
brain (Figure 6B). When the
fecal mass enters the anal canal,
continence receptors in the anal
canal are triggered leading to an
autonomic contraction of the
external anal sphincter. The
continence receptors are located
superficially in the mucosal or
submucosal tissue of the distal
anal canal at one to three
centimeters from the anal verge.
Further filling of the
rectum will eventually result in
urge sensation. At this moment a
person becomes aware of rectal
filling sensations and he can also
voluntarily contract the external
anal sphincter, thus avoiding
involuntary loss of fecal mass.
The continence reflex may be
overruled by the brain by
building up extra pressure in the
abdomen and by relaxation of the
anal sphincter causing the fecal mass to be expelled. So, according to this new understanding,
rectal filling sensations are not directly responsible for fecal continence.
Normally, during waking hours we do not need to think about our fecal continence
because the anal-external sphincter continence reflex is active till urge sensation. When urge
sensation is reached, a person becomes aware of the fact that he needs to go to the toilet and
11
he can consciously contract the external anal sphincter to preserve fecal continence. Thus, the
anal-external sphincter continence reflex is responsible for our fecal continence during the
entire period of sleep and during most of the time that we are awake.
Dysfunction of the anal-external sphincter continence reflex, for example by trauma or
surgery, can lead to fecal incontinence. Patients, who know that they lose stool during
wakefulness, can preserve fecal continence by training themselves to respond to any rectal
filling sensation by immediately going to the toilet. During sleep, however, it is not possible
to directly respond to any rectal filling sensation. These patients, therefore, suffer from fecal
incontinence during sleep.
1.4 Problem definition
The classical understanding is that voluntary contraction of the striated external anal sphincter
is controlled by the pudendal nerve. The new theory about the anal-external sphincter
continence reflex implies that the external anal sphincter is also innervated autonomically. It
is not yet known whether the part of the external anal sphincter that is autonomically
contracted by the anal-external sphincter continence reflex is also innervated by the pudendal
nerve. It is known that patients with pudendal nerve damage can less contract their external
anal sphincter consciously.(12,22) Thus, if the autonomic and conscious contraction of the
external anal sphincter are controlled by the same nerve, the autonomic contraction of the
external anal sphincter should also decrease in patients with pudendal neuropathy.
The question that this study will try to answer is whether the autonomic contraction of
the external anal sphincter is also innervated by the (same part of the) pudendal nerve as the
conscious contraction of the external anal sphincter.
12
2. MATERIAL AND METHODS
2.1 Patients
Retrospectively, we reviewed the medical records of all patients older than seventeen years
who had undergone thorough anorectal function tests between January 2010 and November
2013 (N = 211). We had to exclude 141 patients because the anal sphincter was damaged, or
because the patient also did suffer from polyneuropathy, or because the patient underwent
surgery or sustained trauma in the pelvic area that could have led to damage of the innervating
structures of the external anal sphincter. The criteria for exclusion were: anal sphincter
rupture during childbirth, or episiotomy, or sphincterotomy (N = 24), neurological disorders
(e.g. multiple sclerosis, spinal cord injury, spina bifida, polyneuropathy, N = 23), surgery for
prolapse or perianal fistula (N = 22), hysterectomy (N = 20), surgery for congenital anorectal
malformation or Hirschsprung disease (N = 18), other (e.g. prostatectomy, ileo-anal pouch,
sphincter repair, surgery for hemorrhoids, pelvic floor trauma, mental retardation, anal or
prostate cancer, N = 17), or a combination of the above mentioned exclusion criteria (N = 17).
This study was conducted at University Medical Center Groningen, the Netherlands, in
compliance with requirements of our local Medical Ethics Review Board.
The patients that were included underwent anorectal function tests for several reasons.
Most patients suffered from constipation (N = 24) or fecal incontinence (N = 20). Other
reasons for anorectal function tests were: abdominal or (peri)anal pain (N = 9), chronic anal
fissures (N = 8), rectal prolapse (N = 7), and ulcerative colitis (N = 2). Since most patients
suffered from constipation or fecal incontinence (63%), definition, prevalence, causes and
treatment options of these disorders will be briefly discussed.
2.2 Constipation
Constipation is a very common disease in the general population that can significantly
reduces a patients’ quality of life. Patients with constipation have difficulties with losing their
stool and often suffer from abdominal pain. The prevalence of constipation varies widely
between 2% to 27%, depending on the diagnostic criteria used.(23) In patients older than
sixty-five years the prevalence of constipation rises strongly up to approximately 30%.(24,25)
The diagnostic criteria of constipation are: straining during at least 25% of defecations, lumpy
or hard stools in at least 25% of defecations, sensation of incomplete evacuation for at least
25% of defecations, sensation of anorectal obstruction or blockage for at least 25% of
defecations, manual maneuvers to facilitate at least 25% of defecations (e.g. digital
evacuation, support of the pelvic floor), and fewer than three defecations per week.(26)
Constipation can have many causes including: neurogenic disorders
(e.g. Hirschsprung disease and polyneuropathy), metabolic disorders (e.g. hypothyroidism and
hypokalemia), obstruction of the gastrointestinal tract (e.g. colorectal cancer), endocrine
disorders (e.g. diabetes mellitus), psychiatric disorders (e.g. anorexia nervosa), drugs, irritable
bowel syndrome, and idiopathic disorders (e.g. dyssynergic defecation). The treatment of
constipation depends on the cause, but may consist of patient education, behavior
modification (e.g. biofeedback therapy), dietary changes (e.g. more fibers), pharmacologic
therapy (e.g. laxatives), and/or surgery. Patients with constipation caused by neurogenic
disorders were excluded from this study.
13
2.3 Fecal incontinence
Fecal incontinence is defined as the involuntary loss of fecal mass. It is a common condition
in the community with a prevalence ranging from 2% to 18% (27-31) and rising to 50% in
elderly living in institutions.(32-34) Fecal incontinence can have a significant influence on a
patients’ quality of life. Patients with fecal incontinence suffer embarrassment, shame, and
sometimes depression. Some plan their life around maintaining easy and rapid access to a
toilet and avoid social activities as shopping, going to the cinema or a restaurant.
The pathophysiology of fecal incontinence is usually multifactorial with many
contributing factors such as stool consistency and stool volume, rectal storage capacity,
anorectal sensation, anal sphincter and pelvic floor muscle function, and nervous system
function.(34,35) In younger patients, anal sphincter injuries after vaginal delivery or anorectal
surgery for anal fissures, hemorrhoids or fistulas are the most common factors for developing
fecal incontinence.(36,37) In older patients, fecal impaction leading to overflow incontinence,
anal sphincter degeneration, stroke, dementia, and polypharmacy are risk factors for fecal
incontinence. Furthermore, neurological diseases or injuries can be associated with fecal
incontinence.(36,38,39) The treatment of fecal incontinence is difficult and may include
pharmalogical treatment, biofeedback therapy, sacral nerve stimulation, and/or surgery.
Patients with fecal incontinence caused by neurogenic disorders were excluded from this
study.
2.4 Measuring equipment
During the anorectal function tests we recorded and analyzed the data with solar
gastrointestinal high-resolution manometry equipment (Medical Measurement Systems),
version 8.23.Three different types of catheters were used during the anorectal function tests:
Catheter 1: a Unisensor catheter with an outer diameter of 8F with two circular
electrodes of two millimeters with the center of the two electrodes on ten millimeters
distance. This catheter can electrically stimulate the anal canal.
Catheter 2: a Unisensor K12981 solid state (Boston type) circumferential catheter with
an outer diameter of 12F. This catheter measures circumferential pressure every eight
millimeters over a total length of 6.8 centimeters into the rectum (Figure 7).
Catheter 3: a Unisensor K14204 catheter with an outer diameter of 14F with only two
microtip sensors to connect the rectal balloon, to inflate it, and to register the pressure inside
the balloon (Figure 7). The solar gastrointestinal high-resolution manometry equipment
corrected the pressure inside the balloon for the resistance of the balloon itself, so that only
the real pressure of the rectum was reported.
2.5 Anorectal function tests
All anorectal manometries were performed by a single experienced nurse. I have attended
several measurements to get a good picture of the used tests.
14
Anal electrosensibility test
For this test catheter 1 was inserted into the anal canal with the patient in the left lateral
recumbent position. Then the anal canal was stimulated on every centimeter (5-1 centimeters)
from 1 mA till 20 mA with steps of 1 mA. The minimal stimulation being felt by the patient
was reported. With this test the sensibility of the anal canal can be measured. If the
electrosensibility is raised, the patient suffers from pudendal neuropathy. Normal values in the
anal canal at one and two centimeter are ≤ 4 mA.(40) Since the length of the anal canal differs
between subjects, we have chosen to compare the different variables with the
electrosensibility at one centimeter, because everyone has an anal canal with a length of one
centimeter.
Anorectal pressure test
For this test catheter 2 was inserted into the anal canal with the patient in the left lateral
recumbent position. The catheter was carefully fixed to the buttocks near the anal canal with
adhesive tape to prevent slippage during the procedure. During this test basal rectum pressure
and basal sphincter pressure were measured. These are the pressures in the rectum and anal
canal when the patient is at rest. After this, the patients were asked to squeeze to determine
maximum sphincter contractility, i.e., conscious contraction of the external anal sphincter. At
last, a collapsed, non-latex balloon was connected to catheter 3 and placed in the rectum next
to catheter 2. With these two catheters the recto-anal inhibitory reflex could be measured by
registration of the anal canal pressure after dilatation of an anal balloon with air.
The results of the anorectal pressure test can be used to determine whether the patient
has normal resting pressures. Abnormal resting pressures may indicate a medical condition.
For example, patients with anal fissures often have increased basal sphincter pressures caused
by internal anal sphincter spasms.(41) Furthermore, the results can be used to determine
whether the conscious contraction of the external anal sphincter is sufficient. A decreased
maximum sphincter contractility, which is often seen in patients with fecal incontinence, can
be a sign of pudendal neuropathy or external anal sphincter damage. At last, the recto-anal
inhibitory reflex, whereby the internal anal sphincter relaxes in response to increased pressure
in the rectum, is measured. This reflex is absent in patients with Hirschsprung disease, a
disorder in which (parts of) the gastrointestinal tract have no nerves and therefore cannot
function, resulting in constipation and megacolon.(42)
Balloon retention test
With the patient lying in the left lateral recumbent position and using adhesive tape to prevent
slippage during the procedure, we carefully attached catheter 2 to the patient’s buttocks near
the anal canal. Next to catheter 2 we connected the collapsed, non-latex balloon to catheter 3
and placed it in the rectum. After installing the catheters, we administered the test with the
patient sitting upright on a commode. As soon as the patient was completely at ease we very
slowly filled the balloon with water of 37°C (1.0 mL/second). Meanwhile, we recorded the
pressure in the rectal balloon and the volume inflated. We asked the patient to retain the
balloon as long as possible and to report first sensation (some rectal feeling), constant
sensation (at home the patient would now go to the toilet), urge sensation (the patient would
go to the toilet first before continuing any other activity), and maximum tolerable sensation
level. We stopped the test when the patient reached maximum tolerable sensation, i.e., when
filling reached the limit of tolerance, or if the patient had lost the balloon prior to reaching this
limit, i.e., maximum retainable volume. Then we emptied the balloon completely. This testing
technique has been described previously. It provides information about the extent to which the
15
patient experiences rectal filling, rectal capacity, rectal compliance, and whether the anal
canal responds to rectal filling by squeezing.(43-45) The pressure in the anal canal measured
during the entire test represents the autonomic control of the external anal sphincter. So, the
pressure in the anal canal at maximum tolerable or retainable sensation represents the
maximum autonomic contraction.
Defecometry
For this test we used the same type of catheters and the patient was again seated upright on a
commode as in the balloon retention test. First, we filled the balloon with 50 mL of water at
body temperature. We then asked the patient to evacuate the balloon. At this point, the nurse
left the room for the sake of the patients’ privacy. If the patient was unable to expel the
balloon within one minute, the volume of water in the balloon was increased with 50 mL until
the urge sensation volume, measured earlier during the balloon retention test, was reached.
While the patient tried to evacuate the balloon, we measured maximum rectal pressure,
maximum anal sphincter pressure, and the time needed for evacuation. These variables
provide insight into the parameters involved in the defecation process and enable us to assess
whether the patient’s coordination of the anal and pelvic muscles during defecation is
appropriate.(46) If this is not the case the patient suffers from dyssynergic defecation, a
condition whereby an involuntary and paradoxical contraction of the external anal sphincter
and the puborectal muscle occurs, leading to function neuromuscular obstruction and
constipation.(18)
2.6 Statistical analysis
We analyzed the data with SPSS for Windows, version 20.0 (IBM Corp, Armonk, NY.) The
results of the anal electrosensibility test, anorectal pressure test, and balloon retention test
were analyzed. Because the number of patients was small we used nonparametric tests. Thus,
we reported median, minimum, and maximum values or number and percentages. The Mann
Whitney-U test was used to compare the results of the pudendal neuropathy group and the
group without pudendal neuropathy. Multiple and simple linear regression analyzes were
performed to determine the influence of pudendal neuropathy and aging on conscious
sphincter contractility (i.e. maximum sphincter contractility) and autonomic sphincter
contractility (i.e. pressure in the anal canal at maximum tolerable or retainable sensation).
Statistical significance was defined as P ≤ .05.
16
3. RESULTS
3.1 Patient characteristics
After exclusion, the data of seventy patients remained for analysis. The patients were divided
into two groups. The first group consisted of patients who did not suffer from pudendal
neuropathy, i.e., an electrosensibility in the anal canal at one and two centimeter ≤ 4 mA
(N = 17). The second group consisted of patients who did suffer from pudendal neuropathy,
i.e., an electrosensibility in the anal canal at one and two centimeter > 4 mA (N = 53).
Table 1 contains the patient characteristics. Of the seventy patients 76% had pudendal
neuropathy. Most patients in the pudendal neuropathy group were female (66%) and their age
varied from 18 to 81 years (median 60 years). In the group without pudendal neuropathy, 71%
was female with an age between 18 and 72 years (median 41 years). The patients with
pudendal neuropathy were significantly older than the patients without pudendal neuropathy
(P = .013). Furthermore, because the patients were divided into two groups based on their
electrosensibility, it can be seen that the electrosensibility at one, and two centimeter in the
anal canal was significantly higher in patients with pudendal neuropathy compared with
patients without pudendal neuropathy (P < .001).
Table 1. Patient characteristics
No pudendal
neuropathy
Mann
Whitney-U
Pudendal
neuropathy
Patient
characteristics
Number of patients 17 (24%) 53 (76%)
Female 12 (71%) NS 35 (66%)
Age (years) 41 (18-72) .013 60 (18-81)
Anal
electrosensibility
test
Electrosensibility at 1 cm 4 (3-4) <.001 6 (2-20)
Electrosensibility at 2 cm 3 (2-4) <.001 6 (3-20)
Data presented as number (%) or median (range)
3.2 Results anorectal function tests
Table 2 shows the results of the anorectal pressure test. The basal sphincter pressure was
significantly lower in patients with pudendal neuropathy compared with patients without
pudendal neuropathy (median: 50 versus 70 mmHg, P = .027). The maximum sphincter
contractility, i.e., the conscious sphincter contractility, was also significant lower in the
pudendal neuropathy group compared with the group without pudendal neuropathy (median:
165 versus 235 mmHg, P = .007).
17
The results of the balloon retention test show that there were no differences between
the patients with and without pudendal neuropathy at the beginning of the test
(median: 78 versus 118 mmHg). There were also no differences between the two groups in
pressure in the anal canal at maximum tolerable or retainable sensation, i.e., the autonomic
sphincter contractility (median: 135 versus 153 mmHg, Table 2).
Table 2. Results of anorectal function tests
No pudendal
neuropathy
Mann
Whitney-U
Pudendal
neuropathy
Anorectal
pressure
test
Basal sphincter pressure (mmHg) 70 (45-105) .027 50 (20-115)
Maximum sphincter contractility
(mmHg)
= Maximum conscious contraction
235 (115-420) .007 165 (45-430)
Balloon
retention
test
Pressure anal canal at start (mmHg) 118 (20-240) NS 78 (5-310)
Pressure anal canal at MTV/MRV
(mmHg)
= Maximum autonomic contraction
153 (35-250) NS 135 (40-360)
Data presented as number (%) or median (range)
MTV = maximum tolerable volume, MRV = maximum retainable volume
Figure 7 shows anal
electrosensibility at one
centimeter in the anal canal
compared to age. In this graph
it can be seen that patients
with pudendal neuropathy
were older than patients
without pudendal neuropathy
(P = .013). Furthermore, it
demonstrates that patients
with pudendal neuropathy had
a higher electrosensibility
than patients without
pudendal neuropathy.
The maximum
sphincter contractility, i.e.,
conscious contraction of the
external sphincter, is
compared to anal
electrosensibility at one
centimeter in the anal canal in
figure 8A. It becomes clear
that maximum sphincter
contractility decreased if anal
Figure 7. Anal electrosensibility at one cm in the anal canal in
comparison to age. The anal electrosensibility at one centimeter in
the anal canal declined with aging. This can partly be explained by
the fact that patients with pudendal neuropathy were significantly
older than patients without pudendal neuropathy.
18
Figure 8. Conscious (A) and autonomic (B) control of the external anal sphincter. A: The conscious
control of the external sphincter decreased if the anal electrosensibility declined. So, patients with
pudendal neuropathy can less contract their external sphincter consciously. B: In contrast, the autonomic
control of the external sphincter did not decrease if the anal electrosensibility declined. Thus, despite the
pudendal neuropathy these patients can still contract their external sphincter autonomically. MTV =
maximum tolerable volume, MRV = maximum retainable volume
electro-sensibility declined.
This corresponds to the
results of table 1 that
demonstrates that patients
with pudendal neuropathy
had a significantly lower
maximum sphincter
contractility than patients
without pudendal neuropathy
(median: 165 versus 235
mmHg, P = .007).
On the other hand,
figure 8B shows that
pressure in the anal canal at
maximum tolerable or
retainable sensation, i.e.,
autonomic contractility, did
not decrease, as anal
electrosensibility at one
centimeter in the anal canal
declined. This can also be
seen in table 1 which shows
that at the moment of
maximum tolerable or
retainable sensation the
pressure in the anal canal
was 135 mmHg in the group
without pudendal neuropathy
and 153 mmHg in the group
with pudendal neuropathy.
Furthermore, the
results also demonstrates that
there was no relation
between maximum sphincter
contractility, i.e., the
conscious control, and
pressure in the anal canal at
maximum tolerable or
retainable sensation, i.e.,
autonomic control, in
patients with and without
pudendal neuropathy (Figure
9).
A
B
19
Figure 9. Conscious control of the external sphincter in
comparison to autonomic control. There was no relation
between conscious and autonomic control of the external
sphincter in patients with and without pudendal neuropathy
(R2 = .078). MTV = maximum tolerable volume, MRV =
maximum retainable volume.
At last, maximum
sphincter contractility was
compared to the age of the
patients because patients with
pudendal neuropathy were
significantly older than patients
without pudendal neuropathy
(Figure 10). Clearly, the
maximum sphincter contractility
decreased with aging as the line
of the group without pudendal
neuropathy shows. The maximum
sphincter contractility of patients
with pudendal neuropathy,
however, decreased even more
with aging.
3.3 Linear regression analysis
Multiple linear regression analysis
was performed to predict
maximum sphincter contractility,
i.e., conscious contractility, from
age and pudendal neuropathy.
These variables significantly
predicted maximum sphincter
contractility, F(2,67) = 6.77,
P = .002, R2 = .168. Both
variables added significantly to
the prediction, P < .05 (Table 3).
Multiple and simple linear
regression analyzes were also
performed with pressure in the
anal canal at maximum tolerable
or retainable sensation as
dependant variable. The analyzes
showed that age and pudendal
neuropathy did not significantly
predicted pressure in the anal
canal at maximum tolerable or
retainable sensation, i.e.,
autonomic contraction.
Figure 10. Conscious control of the external sphincter in comparison to age. Patients without
pudendal neuropathy show that conscious control of the external sphincter decreased with aging.
However, conscious control of the external sphincter in patients with pudendal neuropathy decreased
even more.
20
Table 3. Results of multiple linear regression analyzes
Dependant variable Variable B SE B Beta P
Maximum sphincter
contractility
= Maximum conscious
contraction
Constant 296.73 31.49 .000
Age (years) -1.34 .59 -.27 .025
Pudendal neuropathy (no/yes) -50.74 24.50 -.24 .042
Pressure anal canal at
MTV/MRV
= Maximum autonomic
contraction
Constant 149.81 30.15 .000
Age (years) -.07 .57 -.02 .908
Pudendal neuropathy (no/yes) 6.98 24.18 .04 .774
Dependant variable maximum sphincter contractility: R2 = .168, F(2,67) = 6.77, P = .002
Dependant variable pressure anal canal at MTV/MRV: R2 = .036, F(2,65) = .042, P = .959
MTV = maximum tolerable volume, MRV = maximum retainable volume
21
4. DISCUSSION
4.1 Discussion
To date, little is known about the innervation of the external anal sphincter, despite the
clinical relevance. The current understanding is that the striated external anal sphincter is
consciously innervated by the inferior rectal nerve branches of the pudendal nerve that arises
from S2 to S4.(47) In some subjects, it was found, that the external anal sphincter is also
innervated directly by the fourth sacral nerve of the sacral plexus.(48) Recently, it was
demonstrated that the component of fecal continence mediated by contraction of the external
anal sphincter depends on a spinal cord reflex, the anal-external sphincter continence reflex,
without influence from the brain.(21) The aim of this study was to test whether the part of the
external anal sphincter that is autonomically contracted by the anal-external sphincter
continence reflex, is also innervated by the pudendal nerve.
The electrosensibility at one and two centimeter in the anal canal was significantly
higher in patients with pudendal neuropathy compared with patients without pudendal
neuropathy (P < .001). This is because we divided the patients in two groups based on their
electrosensibility in the anal canal at one and two centimeter.
Our results confirmed that patients with pudendal neuropathy can less contract their
external anal sphincter consciously, while the autonomic contraction of the external sphincter
is unaffected. The conscious contractility of the external anal sphincter was significantly
lower in patients with pudendal neuropathy compared with patients without pudendal
neuropathy (165 versus 235 mmHg, P = .007). The autonomic contractility of the external
anal sphincter did not differ between the two groups (135 versus 153 mmHg). So, the
autonomic contraction of the external anal sphincter seems to be innervated by another nerve
(branche) as the conscious contraction, maybe not even by the pudendal nerve. This finding
was confirmed by the results that showed that there was no relation between the conscious
and autonomic contraction of the external anal sphincter in patients with and without
pudendal neuropathy (Figure 9).
A limitation of our study was that patients with pudendal neuropathy were
significantly older than patients without pudendal neuropathy (60 versus 41 years, P = .013).
This could be explained by the fact that pudendal neuropathy often develops later in life. It is
known that maximum sphincter contractility decreases with age.(40) Thus, the difference in
conscious contractility of the external anal sphincter between the two groups could also be
caused by the age difference instead of the pudendal neuropathy. In figure 10, however, it can
be seen that the maximum sphincter contractility decreased a lot more in the pudendal
neuropathy group than in the group without pudendal neuropathy. The decrease in maximum
sphincter pressure in patients without pudendal neuropathy is caused by aging, while the
stronger decrease in patients with pudendal neuropathy is caused by pudendal damage.
Furthermore, because of the significant age difference between the two groups a
multiple linear regression analysis was performed. The results demonstrated that pudendal
neuropathy and age significantly predicted maximum sphincter contractility, i.e., conscious
contraction, but not pressure in the anal canal at maximum tolerable or retainable volume, i.e.,
autonomic control. A simple linear regression analyses demonstrated that age and pudendal
neuropathy alone did also not predict autonomic contractility. So, it can be concluded that the
significant difference in the conscious contractility of the external anal sphincter between the
22
two groups can not only be explained by the significant higher age of the pudendal
neuropathy group, because age and pudendal neuropathy both significantly predicted
maximum sphincter contractility. Besides that, these results support the hypothesis that the
autonomic contraction of the external anal sphincter is innervated by another nerve as the
pudendal nerve, since pudendal neuropathy did not influence the autonomic contractility. We
do not know yet why aging had no influence on the autonomic contraction of the external
sphincter, while it did significantly affect the conscious contraction. This matter needs to be
investigated in more detail.
It should also be kept in mind that it is not clear how anal electrosensibility testing
precisely works, because it is unknown which receptors are stimulated during the test.(49)
Besides that, Felt-Bersma et al. demonstrated that there was no correlation between anal
sensitivity and pudendal nerve terminal motor latency time, which measures the motor
function of the pudendal nerve.(50) Despite that, the technique has been shown to be a
reliable and repeatable test of anal sensation and it is known that the pudendal nerve supplies
the sensory innervations of the lower part of the anal canal.(19,49)
At last, we found that basal sphincter pressure was significantly higher in patients
without pudendal neuropathy compared with patients with pudendal neuropathy
(70 versus 50 mmHg, P = .027). We can not yet explain why patients without pudendal
neuropathy had a raised basal anal pressure compared to patients with pudendal neuropathy
and compared to healthy subjects, therefore, more research is necessary.
Support for our hypothesis comes from the observations reported by Stefanski et al.
They found that the pudendal nerve is not necessarily the only source of external anal
sphincter innervation. In nineteen of one hundred ten preparations of the pudendal nerve and
its branches in fetuses, the external anal sphincter was also innervated directly by the fourth
sacral nerve of the sacral plexus.(48) So possibly, the autonomic contraction of the external
anal sphincter might be innervated directly by the fourth sacral nerve of the sacral plexus.
More research, however, among others in adult cadavers, will be necessary to exactly
determine which nerve (branche) is responsible for the autonomic innervation of the external
anal sphincter.
4.2 Clinical relevance
Earlier research demonstrated the existence of the anal-external sphincter continence reflex.
This reflex is responsible for fecal continence during sleep and most of our waking hours.
When the anal-external sphincter continence reflex is active, we do not need to think about
our fecal continence, until urge sensation is reached and a person becomes aware that he/she
needs to go to the toilet. At that moment, conscious contraction of the external anal sphincter
can prevent loss of stool.(21) Patients with pudendal neuropathy, however, can no longer
contract their external anal sphincter consciously and therefore will suffer from fecal urge
incontinence. The good news might be that patients with (limited) pudendal nerve damage can
preserve fecal continence during waking hours by training themselves to respond to constant
rectal filling sensation by immediately going to the toilet. Thus, these patients will preserve
fecal continence by autonomic contraction of the external anal sphincter. On the other hand,
dysfunction of the nerve that innervates the autonomic part of the external anal sphincter will
result in fecal incontinence (far) before urge sensation will be reached. It is therefore
important that it becomes clear which nerve (branche) is responsible for the autonomic
innervation of the external anal sphincter to prevent nerve damage during surgery.
23
4.3 Conclusion
Our results support the conclusion that the autonomic contraction of the external anal
sphincter is innervated by another nerve (branche) as the conscious contraction, presumably
not even by the pudendal nerve. It is not yet known which nerve is responsible for the
autonomic contraction of the external anal sphincter. A possibility might be that it is
innervated directly by the fourth sacral nerve of the sacral plexus. More research, however, is
necessary to determine precisely which nerve (branche) innervates the autonomic contraction
of the external anal sphincter.
24
5. ACKNOWLEDGMENTS
I would like to express my great appreciation to Dr. P.M.A. Broens, my research
supervisor, for his advice, time, and useful suggestions during this study. Most important,
however, was his enthusiastic encouragement. I would also like to thank Mrs. O.J. Pras
for here substantial assistance in the manometry laboratory.
25
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