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

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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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