Download Disorders of gastrointestinal motility: Towards a new classification1

Journal of Gastroenterology and Hepatology (2002) 17 (Suppl.) S1–S14
WORKING PARTY REPORT
Disorders of gastrointestinal motility: Towards a new classification1
DAVID WINGATE,* MICHIO HONGO, † JOHN KELLOW, ‡ GREGER LINDBERG § AND
ANDRÉ SMOUT ¶
*Barts & The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK,
Department of Comprehensive Medicine, Tohoku University, Sendai, Japan, ‡Department of Gastroenterology,
Royal North Shore Hospital, University of Sydney, Sydney, Australia, §Department of Medicine, Huddinge
University Hospital, Karolinska Institute, Stockholm, Sweden and ¶Department of Gastroenterology, Utrecht
University Hospital, Utrecht, The Netherlands
†
INTRODUCTION
Although gastrointestinal motor activity has been
studied for more than a century, the identification of
motor disorders in clinical practice still presents problems. Over the last two decades, the conventional taxonomy of motor disorders, even assuming that such a
classification exists, has been challenged by the realization that disorders of neural control of motor activity
are, or may be, accompanied by altered visceral sensation. It is now accepted that symptoms of disordered
function such as ‘spasm’, traditionally interpreted by
patients and physicians alike as representing abnormal
motor events, may be caused by the abnormal sensory
representation of normal motor activity. The increasing
substitution of the term ‘neurogastroenterology’ for
‘motility’ implies recognition that the motor activity of
the gut is determined by its innervation and, even more
important, that the gut has both a sensory and a motor
innervation. When the nerves controlling the gut are
damaged, the damage may affect both motor and
sensory domains; even when it is confined to one
domain, the altered function in that domain may induce
alterations in the other domain.
Reliance on symptoms as indicators of disease entities has, with the advance of diagnostic technology,
almost disappeared in many branches of medicine. But
the motor activity of the digestive tract is hidden, and
difficult to detect and define and, in this field of gastroenterology, symptoms are often all, or nearly all, that
can be learnt from the patient. In the last decade, the
‘Delphic’ technique has been used to try and define
combinations of symptoms in the belief, or hope, that
specific symptom patterns correspond to specific
underlying disorders. The ‘Rome criteria’ for the definition and diagnosis of functional gastrointestinal
disorders have received much attention. Unfortunately,
consensus of opinions by experts does not, per se,
confer scientific validity. Evidence-based medicine
requires not consensus, but evidence.
We have reappraised the problem of classifying motor
disorders by relying on what can be established by the
detection of abnormal motor patterns, usually, but not
invariably, associated with the altered movement of the
contents of the digestive tube. In some, but not yet all,
disorders, this approach is reinforced by identification
of underlying pathological change in enteric innervation
or musculature. While we remain aware that the association between symptoms—the perception that drives
patients to seek help—and motor abnormalities is not
always clear, we have taken the view that objectively
reproducible alterations in organ function provide a
robust basis for taxonomy. Such problems are not
unique to gastroenterology; as an example, the association between dyspnea and specific pulmonary pathologies is not always clear, but dyspnea is a useful
indication of abnormal respiratory function indicative
of disease.
Clinicians may feel dismayed that we have not elected
to define two commonly used terms: ‘functional dys-
Correspondence: Professor David Wingate, The Wingate Institute, 26 Ashfield Street, London E1 2AD, UK.
Email: [email protected]
1
Working Team Report prepared for Organization mondiale de gastroenterologie (OMGE).
© 2002 Blackwell Science Asia Pty Ltd
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pepsia’ and ‘irritable bowel syndrome’ (IBS), as diagnostic entities of motility disorder. These two terms are,
like ‘chronic fatigue syndrome’, analogous to phrases
such as ‘bad weather’. Their broad meaning is widely
understood, but they are insufficiently precise to indicate anything other than cohorts of patients who complain of symptoms, in the upper and lower abdomen,
that do not appear to be attributable to organic disease.
Similar problems bedevil the division of such disorders
into different subtypes. ‘Constipation-predominant’
IBS and ‘diarrhea-predominant’ IBS cannot be defined
with precision; these terms are ways in which patients
describe their symptoms, but it is debatable whether
such terms refer to different underlying disorders (often
unlikely as a patient may alternate between these
symptom patterns) or different manifestations of a
single pathophysiology. Such categories of classification
have a pragmatic value in clinical practice because they
identify the presenting symptoms, but the assumption
that they correspond to specific abnormalities of gut
motor function is unjustified. We propose a new diagnostic term, namely ‘enteric dysmotility’. In clinical
practice, we identify patients who have the manometric
characteristics of intestinal pseudo-obstruction, but
lack other features of pseudo-obstruction, such as
dilated small bowel or delayed bowel transit. Such
patients may be in the category of pseudo-obstruction
that is marked by relapses and remissions; even in
remission, the motor abnormalities persist. But there
are also patients in whom the disease process, be it neuropathy or myopathy, is tending towards frank pseudoobstruction, but has not yet reached that point. Finally,
while intestinal manometry is rarely performed in
patients at present categorized as ‘irritable bowel syndrome’, the experience of ourselves and others leads us
to hypothesize that a significant fraction of the cohort
of patients currently labeled as IBS would, if studied
manometrically, be shown to have manometric markers
of neuropathic or myopathic damage. For all of these
reasons, the label of ‘enteric dysmotility’ would seem to
serve a useful purpose.
Symptoms usually suggest a regional focus of abnormal function, and this may be confirmed by clinical
investigation. Physicians need to be aware that the
causes of such abnormalities may be due to systemic
rather than local disease. The lesions of progressive systemic sclerosis may be found in both the esophagus and
the small intestine, but the changes in only one of these
organs may give rise to symptoms. Our classification is
regional, because, in general, this is how such disorders
present in the clinic, but we have indicated where possible systemic causes for motor dysfunction should be
suspected, as the underlying disease may be amenable
to therapy.
In the present report, we have chosen to present our
conclusions in tabular form. The first table lists investigative techniques that we consider to be the essential
diagnostic armamentarium for the diagnosis of gastrointestinal motor disorders.The second table presents
a regional classification of motor dysfunctions, which
we have grouped according to the strength of the
evidence that they are markers of pathophysiology.
The third table summarizes the effects of damage at
D Wingate et al.
different levels of neural control of the gut, as a
reminder that there is little that can be deduced
about the locus of neuropathology from symptoms
alone. The tabular material is supported by a commentary that explains some of the reasoning underlying our
classification.
We have not included a comprehensive bibliography
of the entire field, not least because there are numerous
subject reviews that list this material; we have confined
literature citations to evidence that supports our conclusions. We are aware that this selective use of the literature is open to criticism, but, while we acknowledge
the importance of ‘evidence-based medicine’, in reality
the ‘evidence’ is often equivocal. This is hardly surprising, as the hypotheses that drive research are often generated not by mere scientific curiosity, but by beliefs
that are already deeply rooted. The published evidence
in this field, as elsewhere, can be adduced to support
different and contradictory conclusions. In all humility,
we suggest that the validity of our classification will be
tested in the arena of clinical practice that has informed
our own collective judgement.
DIAGNOSTIC METHODS
In Table 1, we have listed what we consider to be the
clinical investigations that are of established and, so far,
Table 1
Diagnostic methods
1. ESOPHAGUS
Imaging
Fluoroscopy with radiopaque fluid media
Fluoroscopy with barium-impregnated solids (bread,
marshmallow)
pHmetry
24-h monitoring
Manometry
Station pull-through or sleeve sensor manometry
2. STOMACH
Imaging
Gamma-scintigraphy (99technetium-labeled meal)
3. BILIARY TRACT
Manometry
Station pull-through manometry of sphincter of Oddi
4. SMALL INTESTINE
Imaging
Fluoroscopy with radiopaque fluid media
Manometry
24-h proximal small bowel manometry
5. COLON & ANORECTUM
Imaging
Serial radiographs of ingested solid radiopaque markers
Defecating proctography
Manometry
Anorectal function test
Gut dysmotility: A new classification
enduring value in the diagnosis of gastrointestinal
motor disorders. The listed techniques are those that
we consider should be generally available in clinical departments that offer a diagnostic service for gut motor
disorders. Innovative new techniques devised by active
research workers, such as the barostat, or the use of
methods such as ultrasound and electrical impedance,
are frequently advocated for use in clinical practice.
While such techniques have yielded valuable data on
normal and abnormal physiology, at the time of writing
they have not been shown to produce useful clinical
information for the management of patients that cannot
be obtained more easily and at less cost using established methods.
There are three omissions from the list that deserve
comment. Antral manometry has provided valuable
insights into the pathophysiology of gastroduodenal
motor disorders, but the information provided by
gastric scintigraphy on the dynamics of gastric emptying is clinically more useful, less stressful for patients,
and clearly superior in terms of cost-benefit, since
gamma cameras are standard hospital equipment in the
developed world. The lactulose breath test is an elegant
and useful index of small bowel transit in the healthy
subject, but not in patients with motor disorders in
which bacterial overgrowth of the distal small bowel
may occur, as premature bacterial metabolism of the
substrate in the small bowel negates the validity of the
test for the measurement of orocecal transit. Electrogastrography is a technique that has attracted some
because of its non-invasive nature and utilization of
digital technology; it is not labor intensive, and the unit
cost per study is low. As we indicate below, however, we
believe that its diagnostic value remains unproven.
One inclusion also deserves comment. The follow-through barium meal for assessing small bowel
transit is certainly imprecise, and its value depends
upon the diagnostic skill of the radiologist. But it
may be the essential first step in the diagnosis of disordered small bowel motor activity, and when delayed
transit is detected, it is also an important tool for
distinguishing between mechanical obstruction and
pseudo-obstruction.
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1 Esophagus
1.1.1. Gastroesophageal reflux disease
The Working Team felt that gastresophageal reflux
disease (GERD) should be listed as an esophageal
motility disorder because GERD is primarily caused by
motor dysfunction (i.e. malfunctioning of the dynamic
antireflux barrier that is composed of the lower
esophageal sphincter (LES) and the surrounding
diaphragmatic crus). The argument that the objective
diagnosis of GERD is not made by studying the antireflux barrier, but rather by assessing the consequences
of barrier failure (esophagitis, excessive acid exposure)
does not stand in the way of classifying GED as a motility disorder.
In the past, only patients with identifiable lesions of
the esophageal mucosa (esophagitis, Barrett’s esophagus) were thought to have GERD, but it was later
recognized that endoscopy-negative patients may have
symptoms that are as severe and as typical as those of
patients with esophagitis.1 It should be noted that not
all endoscopy-negative reflux patients have excessive
gastresophageal reflux (as quantified by means of prolonged esophageal pH monitoring) but symptoms may
also be brought about by esophageal hypersensitivity to
acid.2
1.1.2. Achalasia
Eesophageal manometry is the most relevant test for
establishing the diagnosis of achalasia, especially in the
early stages of the disease when the esophagus is still of
normal caliber. The classical manometric signs of achalasia are: incomplete relaxation of the LES upon swallowing, high basal LES pressure, absence of esophageal
peristalsis and an elevated baseline pressure in the
esophageal body. However, not all the classical manometric signs of achalasia may be present in all cases. In
a subset of patients with achalasia, preservation of peristalsis in part of the esophageal body with complete
deglutitive LES relaxation and intact transient LES
relaxation has been reported.3
1.1.3 Eesophageal spasm
MOTOR DISORDERS
The motor disorders of the gastrointestinal tract are
listed in Table 2. Here we list the motor abnormalities
of the gut, and the corresponding clinical entities. We
have also listed the disorders, usually systemic, with
which these abnormalities may be associated. Given the
uncertainties that remain in this developing field of
gastroenterology, we have classified the motor disorders
not only by region, but also in categories according to
the degree of certainty in terms of correspondence with
symptoms that we consider appropriate. Clearly, there
is a subjective element to this classification, but it does
represent both a consensus among the authors and, as
far as possible, a concordance with the published literature. In the comments that follow, the numbering
refers to the listing in Table 2.
Esophageal spasm is characterized manometrically by
the intermittent occurrence of simultaneous contractions; for a long time, the criterion of > 10% simultaneous contractions following wet swallows has been
used. In order to differentiate spasm from lowamplitude simultaneous waves seen in other disorders
(such as scleroderma and reflux disease) it is now
recommended4 that, for the diagnosis of esophageal
spasm, a mean simultaneous contraction amplitude of
≥ 30 mmHg is required. In patients with esophageal
spasm, the extent of the esophageal segment in which
simultaneous contractions are found is variable. The
term ‘diffuse’ esophageal spasm has been used to
denote the condition in which the entire length of the
smooth muscle part of the esophagus is affected. There
is no indication that localized spasm is a disease entity
that is different from diffuse spasm.
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Table 2
D Wingate et al.
Motor disorders of the gastrointestinal tract
Demonstrable abnormality
Clinical entity
Associated disorder
1. ESOPHAGEAL DYSMOTILITY
Category 1: Well-defined entities
1.1.1 Excessive acid exposure
GERD
Scleroderma, diabetes mellitus
Achalasia
Chagas’ disease, Enteric neuropathy
Esophageal spasm
Diabetes mellitus, Enteric neuropathy
Nutcracker esophagus
Enteric neuropathy
1.2.2 Low-amplitude peristalsis
Failed peristalsis
Low-amplitude simultaneous contractions
Ineffective esophageal motility
Scleroderma. Enteric myopathy,
Diabetes mellitus, Amyloidosis,
GERD
1.2.3 Low LES pressure
Hypotensive LES
Scleroderma, Diabetes mellitus,
GERD
LES dysrelaxation
Post-fundoplication
1.1.2 Manometric pattern of achalasia
1.1.3 Spastic manometric pattern
Category 2: Entities with variable dysfunction–
symptom relationship
1.2.1 High-amplitude peristalsis
1.2.4 Incomplete LES relaxation
Category 3: Questionable entities
1.3.1 High LES pressure
Category 4: Entities associated with behavioral
disorders
1.4.1 Forced regurgitation
Hypertensive LES
Rumination syndrome
Anorexia nervosa (purging type),
Bulimia nervosa (purging type)
Aerophagia
GERD
2. GASTRIC DYSMOTILITY
Category 1: Well-defined entities
2.1.1 Accelerated gastric emptying
Dumping syndrome
Post-resection dumping, Postvagotomy dumping
Category 2: Entities with variable dysfunction–
symptom relationship
2.2.1 Delayed gastric emptying
Gastroparesis
GERD, Diabetes mellitus,
Scleroderma, Post-vagotomy. Enteric
neuropathy, Enteric myopathy,
Anorexia nervosa (restricting type)
Gastric dysrelaxation
Diabetes mellitus, Post-vagotomy
Tachygastria
Motion sickness, Nausea of
pregnancy
Forced vomiting
Anorexia nervosa (purging type),
Bulimia nervosa (purging type)
1.4.2 Excessive air swallowing
Excessive belching
2.2.2 Impaired adaptive relaxation
Category 3: Questionable entities
2.3.1 High-frequency gastric electrical control
activity
Category 4: Entities associated with behavioral
disorders
2.4.1 Self-induced vomiting
3 BILIARY TRACT DYSMOTILITY
Category 1: Well-defined entities
None
Category 2: Entities with variable dysfunction–
symptom relationship
3.2.1 High basal pressure of biliary sphincter
(± high-frequency sphincter contractions)
Spincter of Oddi dyskinesia
Gut dysmotility: A new classification
Table 2
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(Continued)
Demonstrable abnormality
Clinical entity
Associated disorder
Category 3: Questionable entities
3.3.1 Impaired gallbladder emptying
Biliary dyskinesia
Gallstone disease, Diabetes mellitus,
Post-vagotomy syndrome
Intestinal pseudo-obstruction
Enteric myopathy, Enteric
neuropathy, Scleroderma
Enteric dysmotility
Enteric neuropathy, Enteric
myopathy, Post-vagotomy syndromes,
Parkinson’s disease, Scleroderma,
Diabetes mellitus, Rare endocrine &
metabolic disorders, Spinal injury
Intestinal hurry
Rare endocrine & metabolic
disorders, Post-vagotomy syndrome
Ogilvie’s syndrome
Megacolon
Enteric myopathy, Enteric neuropathy
5.1.2 Absent rectoanal inhibitory reflex
Hirschsprung’s disease
Enteric neuropathy
5.1.3 Delayed colonic transit
Slow transit constipation
Enteric neuropathy, Enteric
myopathy, Parkinson’s disease,
Endocrine disorders, Spinal injury
Category 4: Entities associated with behavioral
disorders
None
4 SMALL INTESTINAL DYSMOTILITY
Category 1: Well-defined entities
4.1.1 Abnormal contractile activity with episodic
or chronic signs mimicking mechanical
obstruction
Category 2: Entities with variable dysfunction–
symptom relationship
4.2.1 Abnormal contractile activity and/or
delayed small bowel delayed
Category 3: Questionable entities
4.3.1 Accelerated transit
Category 4: Entities associated with behavioral
disorders
None
5 COLONIC AND ANORECTAL
DYSMOTILITY
Category 1: Well-defined entities
5.1.1 Dilated colon (diffuse, segmental)
with/without dilated small bowel
Category 2: Entities with variable dysfunction–
symptom relationship
5.2.1 Abnormally low anal canal pressures
Category 3: Questionable entities
5.3.1 Accelerated transit
Fecal incontinence
Diabetes mellitus, Spinal injury
Colonic hurry
Bile salt malabsorption, Short bowel
syndrome, Rare endocrine &
metabolic disorders
Category 4: Entities associated with behavioral
disorders
5.4.1 Impaired pelvic floor relaxation
Anismus
5.4.2 Avoidance of defecation
Functional fecal retention
GERD, gastroesophageal reflux disease; LES, lower esophageal sphincter.
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1.2.1 Nutcracker esophagus
In this condition, esophageal contractions propagate
normally, but have abnormally high amplitude (more
than 2 standard deviations above the mean value from
a group of normal subjects). Although it has been disputed whether nutcracker esophagus should be considered a clinical entity,5 most experts would feel that there
is reasonable evidence that the abnormality is more
often associated with symptoms (chest pain and dysphagia) than would be expected on the basis of chance.
1.2.2 Ineffective esophageal motility
Traditionally, the primary esophageal motor disorders
were classified as achalasia, diffuse esophageal spasm,
nutcracker esophagus and a ‘left over’ group of nonspecific esophageal motor disorders. As 98% of patients
in this category have ineffective esophageal contractions
(low-amplitude, simultaneous or non-transmitted) it
has been proposed that ‘ineffective esophageal motility’
is a more appropriate term.4,6 More specifically, the
manometric criteria for ineffective esophageal motility
are: at least 30% of wet swallows followed by either peristaltic or simultaneous contractions with an amplitude
< 30 mmHg, or by non-transmitted peristalsis, or by
absent peristalsis. These abnormalities have in common
that they can all lead to impaired esophageal transit of
food and to impaired clearance of refluxed material.
The amplitude threshold of 30 mmHg finds physiological justification in simultaneous manometric and
radiographic observations showing that low-amplitude
contraction waves, even if peristaltic, do not clear a
barium bolus from the esophagus.7 Ineffective
esophageal motility is often associated with an hypotensive LES.
1.4.1. Rumination
Rumination is the phenomenon characterized by
repeated postprandial regurgitation of gastric contents
that is brought about by forceful contractions of the
abdominal wall muscles. Rumination may mimic an
esophageal motility disorder but is, in fact, a behavioral
abnormality. Optimal treatment of the rumination
syndrome (behavioral therapy) differs from treatment
of GERD. Rumination can be differentiated from
GERD by means of a study in which intra-abdominal
pressure is monitored simultaneously with intraesophageal pH.
1.4.2. Aerophagia
Aerophagia is a relatively rare condition in which excessive air swallowing leads to excessive and troublesome
belching. Clinically, it is important to differentiate
aerophagia from gastroesophageal reflux disease.
2 Stomach
2.2.1. Gastroparesis
The term gastroparesis is often used to denote delayed
gastric emptying. It is important to realize that the asso-
D Wingate et al.
ciation between the rate of gastric emptying and upper
abdominal symptoms is extremely poor. Therefore, the
term gastroparesis should not be used as a synonym for
dyspepsia or dyspeptic symptoms. Some believe that the
term should be reserved for cases with severely delayed
gastric emptying.
Delayed gastric emptying, with or without associated
symptoms, is a well-known phenomenon in some
chronic conditions, such as diabetes, scleroderma,
postvagotomy state, and chronic idiopathic intestinal
pseudo-obstruction. In patients with functional dyspepsia idiopathic gastroparesis is found more often than
in healthy subjects, but the proportion of patients with
delayed gastric emptying is only 37% and the magnitude of the delay is about 50%.8 These observations
suggest that delayed gastric emptying may be involved
in the pathogenesis of functional dyspepsia, but the
cause–effect relationship is poor.
2.2.2. Gastric dysrelaxation
Using the barostat technique, several groups of investigators have demonstrated that the postprandial increase
in proximal gastric volume (relaxation) is decreased
in patients suffering from dyspeptic symptoms.9,10 A
similar impairment of relaxation was found with an
ultrasonographic technique.11 In addition, scintigraphic
techniques have been used to show that patients with
functional dyspepsia often have an abnormal intragastric distribution of food. In healthy subjects the bulk
of a solid meal accumulates in the gastric fundus, but
in dyspeptic patients a larger proportion of the meal
goes directly to the (distended) gastric antrum.12 Thus,
studies using different techniques appear to indicate
that impaired postprandial relaxation and abnormal
intragastric distribution of meals is a pathophysiological mechanism involved in the genesis of symptoms. In
clinical practice, gastric dysrelaxation is not easily identified using readily available diagnostic methods (fluoroscopy, scintigraphy).
2.3.1 Tachygastria
The gastric antrum generates myoelectrical activity
that can be studied non-invasively by means of surface
recording (electrogastrography (EGG)). However, in
the stomach, the relationships between electrical and
mechanical activities are very complex and electrogastrography cannot be used to assess gastric motility and
emptying.While it has been shown that episodes of electrical activity with abnormally high frequency (tachygastria) do exist, it has not been shown that tachygastria
is a disease entity. An association between tachygastria
and nausea (pregnancy, motion sickness) has been
demonstrated,13 but it is not clear whether tachygastria
is the cause or the consequence of nausea. Studies using
strict criteria for electrogastrographic detection have
shown that the incidence of dysrhythmias in various
patient groups is low.The uncritical use of commercially
available software for EGG analysis may lead to overdiagnosis of gastric dysrhythmias.14
Gut dysmotility: A new classification
3 Biliary tract
3.2.1. Sphincter of oddi dyskinesia
Because of the variable results of treatment of manometrically proven sphincter dysfunction, we concluded
that biliary dyskinesia should be listed as an entity
with a variable dysfunction-symptom relationship
rather than as a well-defined entity.15,16 In the absence
of stenosis of the sphincter of Oddi, it is questionable
whether sphincterotomy of a sphincter with increased
basal pressure is beneficial for the patient.16
3.3.1. Biliary dyskinesia
Impaired gallbladder emptying is well recognized as
a consequence of inflammatory damage, mechanical
obstruction, and autonomic denervation. But in the
absence of these conditions, it is not clear whether
delayed emptying constitutes a defined clinical
problem.
4 Small intestine
4.3.1 Intestinal pseudo-obstruction
Abnormal small bowel contractile activity, in combination with episodic or chronic signs mimicking mechanical obstruction of the small bowel, is the defining
feature of intestinal pseudo-obstruction. Abnormal
propagation of phase III of the migrating motor
complex (MMC), bursts or sustained periods of uncoordinated contractile activity, absence of a fed pattern
after a meal,17–19 and severe hypomotility20,21 all indicate
an underlying neuromuscular disorder. Severe hypomotility and dilated bowel are seen mainly in patients
with myopathic pseudo-obstruction, whereas uncoordinated and increased contractile activity is the typical
finding in neuropathic pseudo-obstruction.
4.2.1 Enteric dysmotility
The increased use of small bowel manometry in the
clinical investigation of patients with bowel symptoms
has prompted the need for a new diagnostic label to
encompass findings of disturbed motility in patients
without subocclusive events. A good example of this situation is provided by Chagas’ disease. Abnormal small
bowel motility22 and small bowel myenteric plexus neuropathy23 are almost invariably present in gastrointestinal Chagas’ disease, but intestinal pseudo-obstruction
is very uncommon.24 We propose that the term ‘enteric
dysmotility’ should be used instead of symptom-defined
diagnoses whenever abnormal motor activity (contractile activity or transit) can be demonstrated. We believe
that the spectrum of motility disorders may have a
broad but as yet undefined range.The term ‘enteric dysmotility’ also serves the purpose of preventing dilution
of the diagnosis ‘intestinal pseudo-obstruction’ with less
severe cases of dysmotility.
In this area of gastroenterology, the problem with
symptom-based diagnostic categories is that a similar
spectrum of symptoms can be found in multiple
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pathologies.The cardinal symptoms, pain, bloating, and
difficult or disturbed defecation, that characterize ‘irritable bowel syndrome’ also occur in enteric dysmotility
(documented evidence of abnormal contractile activity), and even in neuropathic or myopathic pseudoobstruction. Clinical experience suggests that patients
with these symptoms can be grouped as follows, in
increasing order of clinical severity, disability, and
impaired quality of life:
1. No documented motor abnormality: disorder of
normal function perhaps attributable to visceral hypersensitivity, dietary intolerance, sequelae of acute gastroenteritis etc.
2. Enteric dysmotility: documented abnormal contractile activity, but no past history of episodes, or
current signs, mimicking mechanical obstruction.
3. Pseudo-obstruction: there may be a history
of relapses and remissions, or the condition may be
chronic. Such patients usually require continuous specialist surveillance, and may need nutritional support by
enteral or parenteral feeding.
Because myopathies and neuropathies tend to
become progressively more severe, patients may, over
the course of time, move down the diagnostic categories
from ‘no documented motor abnormality’ to ‘enteric
dysmotility’ and, finally, ‘pseudo-obstruction’.
4.3.1 Intestinal hurry
Accelerated transit through the small bowel may occur
as a result of vagotomy, in particular truncal vagotomy
in combination with pyloroplasty. The main mechanisms leading to diarrhea in patients with vagotomy
seem to be absent25 or temporally reduced26 fed motor
activity after a meal. Other causes of accelerated transit
are hyperthyroidism27 and neuroendocrine tumors.
The diagnosis of intestinal hurry may be prompted
by a radiologist’s report of significantly accelerated
transit of barium in a follow-through barium meal, even
when there is no associated disorder that would account
for this. In France, the diagnosis of ‘diarrhée motrice’
has been applied to patients presenting with diarrhea
and evidence of intestinal hurry, but there is no English
language equivalent term.
5 Colon and anorectum
5.1.3 Slow transit constipation
In this condition, using either radiopaque markers28 or
scintigraphy,29,30 there is a clearly defined defect in the
overall transit of contents from the proximal colon to
the distal colon and rectum, and in the presence of a
normal colon diameter. The delay in transit appears to
occur as a result of decreased colonic propulsion due
to impaired motor activity,31 as a reduction in the frequency of high amplitude propagated contractions, and
a diminished response to meals, cholinergic agents
and the motor effects of stimulant laxatives. It has also
been suggested that the delay in transit can be due to
increased or uncoordinated distal colon motor activity,
but there is little evidence to support this contention.
An abnormal small bowel contractile pattern can be
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detected in some patients; it is argued by some that
small bowel manometry is an essential preliminary
investigation before considering surgical resection, such
as subtotal colectomy with ileorectal anastomosis, as the
presence of enteric dysmotility (see 4.2.1. above) may
adversely affect the outcome of surgery.This latter point
has not yet been clearly established, and controlled
studies of this controversy present logistical and ethical
problems.
Recently, a reduced number of interstitial cells of
Cajal32 and of colonic enteroglucagon and serotoninimmunoreactive endocrine cells,33 as well as the presence of smooth muscle inclusion bodies,34 have been
reported in patients with slow transit constipation.
These findings support the concept that the disorder
may be related to definite alterations in the enteric
neural plexuses and neurotransmitters.
The term ‘colonic inertia’ has been used for this condition. However, we feel that this is a misnomer, as it
implies that the colon is inactive. It may well be true
that the propulsive motor activity of the colon is diminished in this condition. But, as can happen in neuropathic small bowel pseudo-obstruction, there may be no
diminution in muscle activity, but a change in motor
pattern from propulsive to non-propulsive, or even
obstructive. The term ‘slow transit constipation’ accurately reflects the functional impairment without a
possibly unjustified conclusion on the underlying
pathophysiology.
5.2.1 Fecal incontinence
In this condition, anorectal manometry can help define
functional weakness of one or both sphincter muscles,
and also predict the response to biofeedback training.
Both internal and external anal sphincter pressures can
be measured with a reasonable degree of reproducibility, according to reference ranges for both males and
females; the latter need to be established in individual laboratories. Resting (basal) anal canal pressures,
assessed either by station or rapid pull-through techniques, reflect the tonic activities of both the internal
anal sphincter (IAS) and the external anal sphincter
(EAS), with 75–85% of the pressure derived from the
IAS. The technique of assessing squeeze pressures,
which depend upon the patient’s efforts to contract the
EAS, is poorly standardized.35
In two earlier studies with large sample sizes, the
sensitivity and specificity of anal canal pressures for discriminating fecal incontinence from continent controls
was, for maximum squeeze pressure, 60–92%36 and
78–97%37, respectively; the maximum resting anal canal
pressure appears less sensitive and specific in this
regard. A number of other factors, such as sensory
defects, can be implicated in the pathophysiology of
fecal incontinence and the relationship between these
factors and anal canal pressures is poorly defined.
5.4.1 Anismus
In this condition, on radiopaque marker or scintigraphic
testing, there is normal passage of colonic contents or
D Wingate et al.
markers through the colon but then prolonged storage
in the rectum or rectosigmoid region, in the presence
of a normal rectal diameter.This lack of adequate rectal
evacuation (‘outlet delay’, ‘obstructed defecation’)
appears to occur as a result of impaired pelvic floor
relaxation and/or the inappropriate or even paradoxical
contraction of the pelvic floor and EAS during
attempted defecation.38 It is also called ‘pelvic floor
dyssynergia’. During attempts to defecate, the above
phenomenon narrows the anorectal angle and increases
the pressures of the anal canal, causing evacuation to be
less effective.
In uncontrolled studies, anorectal manometry has
demonstrated that increased rectal pressures during an
expulsion effort are associated with increased, rather
than decreased, pressures in the EAS.39 High resting
anal sphincter pressures with relatively little increment
of squeezed pressures may also be seen.40 If these patterns are present in association with abnormal findings
at defecography, the diagnosis of anismus can be made
more confidently.41 At defecography, failure of the rectoanal angle to open by 15 degrees, at times with an
impression on the posterior wall of the rectum of the
unyielding puborectalis, is taken as evidence to support
the diagnosis of anismus. The presence of an abnormal
anal sphincter electromyogram (EMG), and impaired
balloon expulsion from the rectum, are also supportive
of the diagnosis.
Some patients can have features of both slow transit
constipation and pelvic floor dysfunction and, indeed,
this combination appears to be more common than
either disorder alone, at least in tertiary referral practice. Distinction between the two, or confirmation of the
presence of both, is important because the main therapeutic approaches may differ, and because failure of
rectal evacuation may not respond as well to surgical
therapy as does slow transit constipation.
5.4.2. Functional fecal retention
This is by far the commonest cause of constipation, and
is, among adults, largely confined to women. There are
many contributory factors, including poor training in
childhood or adolescence, inappropriate diet, and ignorance and fear surrounding the act of defecation. The
behavior pattern is facilitated by learned suppression of
the normal urge to defecate induced by rectal filling,
and investigation often reveals diminished rectal sensitivity. The latter deficit, which is learned visceral
hyposensitivity, may be reversed by behavioral training
techniques.
NEUROPATHOLOGY OF MOTOR
DISORDERS
The evolution of the concept of ‘neurogastroenterology’
in the last two decades has reflected a growing comprehension of the complex neural systems that govern
the motor activity of the gastrointestinal tract. Among
the systems of the body, the gut is unique in that it is
regulated by an autonomous nervous system, the
Gut dysmotility: A new classification
enteric nervous system (ENS). But while the operations
that the musculature of the gut wall performs on the
luminal content are not dependent upon central neural
control, the enteric and central nervous systems (CNS)
are linked by sympathetic and parasympathetic pathways, and the systems interact. The CNS regulates,
through the behavioral mechanisms of hunger and
satiety, the ingestion of nutrients and, likewise, the
expulsion of feces is also a behavioral response to signals
from the gut.
These behavioral patterns are, in turn, modified by
learning and by social opportunity.
The neurology of the central and peripheral nervous
systems is reflected in the myriad responses of the skeletal musculature, the somatosensory system, and the
special senses. Deviations from normal patterns of
activity can be mapped in detail by rigorous clinical
examination, enabling accurate deduction of the locus
of pathological lesions. Neurogastroenterology is very
different, for two reasons. First, detailed clinical examination of end organs such as parts of limbs, or segments of the body surface is impossible because of the
inaccessibility of the digestive tube. Second, the enteric
nervous system lacks topographical localization of
neural regulatory structures; there appear to be no specialized nuclei or nerve tracts in the ENS such as exist
in the CNS. To make matters even more difficult, the
conscious representation of the gut (visceral perception)
is very limited, and the symptoms of abnormal neural
control are not only few in number, but do not always
differ from similar symptoms due to other pathologies.
In this respect, a useful paradigm is ‘non-cardiac chest
pain’, a clinical conundrum that reflects the real difficulty of distinguishing between the pain caused by
myocardial ischemia and pain of esophageal origin, and,
in the latter instance, of determining the cause of the
pain.
It is important to appreciate that similar motor disorders of the gut, such as dysphagia or constipation,
may result from lesions at quite different levels of neural
control. In Table 3, we list some of these lesions and
their clinical correlates to illustrate the problem. This
list is, in the present state of knowledge, far from comprehensive, and is likely to become even less so, as
understanding of the neural control of the gut increases.
While our present understanding of these matters will
almost certainly be regarded from the future as rudimentary, it is already important for gastroenterologists
to appreciate the complex neuropathologies that may
determine apparently simple dysfunctions of the digestive tract.
In the comments that follow, the numbering refers to
the listing in Table 3.
1 Autonomic nervous system
In this context, it is important to remember that the
term ‘autonomic nervous system’, as classified by
Langley, refers not only to the sympathetic and
parasympathetic divisions, but also to the third or
‘enteric’ division, now known as the ENS comprising
the myenteric (Auerbach) and submucosal (Meissner)
S9
plexuses. Recent studies indicate that the interstitial
cells of Cajal (ICC) are also involved in the regulation
of motor activity. Interstitial cells of Cajal form a nonneuronal network of excitable cells that act as an interface between nerve and muscle. They are believed to
generate the intracellular electrical fluctuations that are
reflected as the slow waves that determine the timing of
gastrointestinal smooth muscle contraction.42
1.1 Enteric nervous system (motor innervation)
Histopathological abnormalities in the ENS, mostly
characterized by degeneration or congenital defect, are
associated with impaired transit of the luminal contents.
Because the input from postganglionic enteric motor
neurons is largely inhibitory, impaired relaxation is the
characteristic motor consequence of enteric neuropathology, but the clinical correlates of such denervation vary according to the region involved in different
pathologies, as exemplified by the examples cited
below.
Achalasia is marked by the absence of LES relaxation
in response to swallowing. Histological studies show
denegeration or inflammation of the myenteric plexus
at the level of the LES.43,44 Immunohistochemical
studies indicate diminished or absent NADPH
diaphorase activity, a marker for neuronal nitric oxide
synthase45,46 and/or vasoactive intestinal peptide
(VIP);47 these are mediators of LES resting pressure
and relaxation. Peristalsis is impaired in most patients
with achalasia; studies of the innervation of the
esophageal body in this group have revealed neuronal damage. Assessment of extrinsic vagal innervation in achalasics, using the heart rate variability as an
indicator,48 suggested normal function, but contrary
views have been expressed.44,49 The nature of the
pathological change is unknown but inflammatory or
immune mechanisms have been proposed; moreover, it
is not known whether the disease process is identical in
all cases.
Pseudo-obstruction is characterized by impairment
or loss of peristalsis in the small intestine, leading to
stasis, bacterial overgrowth, distension, and malnutrition. While the pathogenesis of pseudo-obstruction is
not as yet fully characterized, two separate categories,
enteric myopathy and enteric neuropathy, are recognized. In the neuropathic small bowel, contractile
activity is often increased, but also disordered and nonpropulsive; in contrast, the myopathic small bowel is
unable to contract. Autonomic neuropathy is commonly
found in children with chronic intestinal pseudoobstruction,50 and histological changes in the interstitial cells of Cajal within the myenteric plexus have been
reported.51
Chagas’ disease, also known as South American
trypanosomiasis, is characterized by widespread autonomic denervation throughout the gut; the heart may
be affected as well. The cause of denervation is thought
to be an antigen–antibody reaction between antibodies
generated by infection with Trypanosoma cruzi and a
surface antigen on autonomic nerves. Mega-esophagus
with achalasia, and megacolon are the main clinical
manifestations, but pseudo-obstruction of the small
S10
Table 3
D Wingate et al.
Neurogastroenterology: Neuropathology of motor disorders
Site of lesion/Affective syndrome
1. AUTONOMIC NERVOUS SYSTEM
1.1 Enteric nervous system (motor innervation)
Achalasia
Pseudo-obstruction
Chagas’ disease
Hirschsprung’s disease
Motor disorder
Impaired or absent peristalsis and/or impaired sphincter relaxation
1.2 Enteric nervous system (sensory innervation)
Lowered activation threshold with inappropriate motor response
1.3 Parasympathetic (vagal & pelvic nerves)
Impaired gastric accommodation, Impaired gastric emptying,
Disordered defecation
1.4 Sympathetic (spinal afferents)
Impaired entero-enteric reflexes, Disordered defecation
2. SPINAL CORD
2.1 Spinal cord injury or tumor
Loss of voluntary control of defecation, Decreased rectal
sensitivity
3. CENTRAL NERVOUS SYSTEM
3.1 Congenital abnormalities
Intestinal pseudo-obstruction, GERD, Rumination, Constipation
3.2 Cerebrovascular accident
Oropharyngeal dysphagia
3.3 Brainstem tumors
Vomiting
3.4 Parkinson’s Disease
Constipation
3.5 Degenerative disorders
Loss of voluntary control of defecation
3.6 Visceral hyperperception
Inappropriate motor response
4 MOTOR DISORDERS WITH UNCERTAIN RELATIONSHIP TO AFFECTIVE SYNDROMES (PSYCHOMOTOR
DISORDERS)
4.1 Depressive disorders
Impaired esophageal peristalsis, Impaired intestinal transit,
Constipation
4.2 Anxiety disorders
Spastic pattern esophagus, High-amplitude peristalsis,
Hypertensive LES, Impaired gastric emptying, Rapid bowel
transit
4.3 Hypochondriasis/somatoform disorder
Disordered defecation
4.4 Stress-induced disorders
Frequent defecation, Delayed gastric emptying
GERD, gastroesophageal reflux disease; LES, lower esophageal sphincter.
bowel is rare, even though histological damage can be
demonstrated.23
Hirschsprung’s disease is a congenital disorder characterized by a solitary narrow segment in the colon
that obstructs colonic transit. Histological studies show
absence of the myenteric plexus within the narrow
segment; loss of relaxation in the aganglionic segment
is the pathophysiological correlate.
1.2 Enteric nervous system (sensory innervation)
Lowered activation threshold of sensory receptors in
the gastrointestinal tract, synonymous with visceral
hypersensitivity, occurs in a variety of disorders. When
it occurs in the esophagus and in the colon, inappropriate motor responses are observed. Spastic
manometric patterns can be detected in some patients
after acid reflux into the esophagus; thus, some cases
of nutcracker esophagus and diffuse esophageal
spasm may be due to visceral hypersensitivity. In
some patients, abnormal reflex motor responses to
electrical mucosal stimulation have been demonstrated;
this phenomenon may explain one characteristic
symptom of the irritable bowel: abdominal pain
accompanied by the urge to defecate and relieved by
defecation.
Gut dysmotility: A new classification
S11
1.3 Parasympathetic (vagal and pelvic nerves)
52
Truncal vagotomy abolishes gastric accommodation,
and impairs gastric emptying of a semisolid meal.53
Similar changes occur in patients with diabetic neuropathy and decreased vagal tone.54
Pelvic neuropathies, both iatrogenic (surgical or
obstetric injury) and neuropathic (idiopathic or diabetic), impair defecation.
1.4 Sympathetic (spinal afferents)
Autonomic neuropathy causes delay in gastric emptying, impaired esophageal motility and prolongation of
intestinal transit time.55 In those patients, constipation
can be the solitary symptom even though widespread
gastrointestinal motor abnormalities are present.
2 Spinal cord
the esophageal body and LES,67 and constipation.67–70
The most significant problem, however, is constipation,
which affects about 70% of patients with the disease.
Gastrointestinal dysmotility may affect the pharmacodynamics of anti-Parkinson’s drugs, but conversely,
some of the gut dysmotility in Parkinson’s disease has
been explained as adverse side-effects of drugs. The
lesions of the disease, in the form of Lewy bodies, have
been found in the esophagus and in the colon, but it
has not been determined whether dysmotility that
occurs is central or peripheral in origin.
3.5 Degenerative disorders
In degenerative disorders such as Alzheimer’s disease,
severe constipation is common. This may be secondary
to loss of voluntary control of defecation; it remains to
be determined whether there is any associated motor
disorder and, if so, whether the underlying disorder of
neural control is central or peripheral.
2.1 Spinal cord injury or tumor
Spinal cord injury or tumor impairs somatosensori-motor functions. Damage to the cervical cord
may cause disordered deglutition and/or decreased
colonic motility.56 Lesions at the lumbosacral level may
induce increased colonic myoelectric activity,57 but this
may be non-propulsive, as spinal cord injuries are associated with retarded colonic transit,58 leading to fecal
impaction or incontinence.56 If voluntary muscle
function is impaired, patients may lose control of
defecation.
3 Central nervous system
3.1 Congenital abnormalities
Congenital abnormalities of CNS may include mental
retardation and spina bifida. In such patients, deglutitive disorders, reflux esophagitis, rumination, intestinal
pseudo-obstruction including idiopathic gastroparesis
and/or severe constipation may occur.59–62 Concomitant
impaired development of ENS and ANS may also contribute to these motor abnormalities along with CNS
abnormalities, but evidence on this is lacking.63
3.6 Visceral hyperperception
Increased afferent input may result in increased efferent
output to cause inappropriate motor response. There
are three possible mechanisms for visceral hypersensitivity. First, receptors in the gut may have a lowered
threshold to local stimuli in the gut; second there may
be an abnormally sensitized afferent pathway; finally,
there may be abnormally sensitive cognition to normal
stimuli at the level of the cerebral cortex. Dynamic
imaging using magnetic resonance or positron emission
tomography has shown increased activation of cortical
centers associated with visceral hyperperception, but, so
far, it has not been possible to identify which of the
three possible mechanisms are responsible.
4 Motor disorders with uncertain
relationship to affective syndromes
(psychomotor disorders)
4.1 Depressive disorders
3.2 Cerebrovascular accident
Gastrointestinal motor activities are suppressed in
patients with depression. Impaired esophageal transit,
delayed gastric emptying, delayed intestinal transit,71
and constipation72 have been reported.
Cerebrovascular accident causes oropharyngeal dysphagia, especially in the acute phase.64 No other disturbances of motor function have been documented.
4.2 Anxiety disorders
Vomiting may be the solitary presenting symptom of a
brainstem tumor, with an absence of any neurological
sign or symptoms.65,66
Patients with a high level of anxiety symptoms often
show a spastic pattern of esophageal contractions
(simultaneous and/or repetitive contractions),73–76 high
amplitude contractions77 and an hypertensive LES.78
Gastric emptying may79,80 or may not81 be delayed,
and intestinal transit can be rapid.71,82
3.4 Parkinson’s disease
4.3 Hypochondriasis/somatoform disorder
Gastrointestinal motor disorders in Parkinson’s disease
include oropharyngeal dysphagia, motor dysfunction of
Hypochondriasis, conversion disorder and somatoform
disorders are closely correlated, and some patients com-
3.3 Brainstem tumors
S12
plain of a variety of symptoms that suggest gastrointestinal motor dysfunction. However, definite motility
disorders that would explain their symptoms are usually
lacking.
4.4 Stress-induced disorders
Psychosocial stress has been shown to perturb the
motor activity of all regions of the gut, from esophagus
to colon. These changes may be mediated by the ANS,
and also humorally by the release of corticotrophin
releasing hormone, especially in IBS patients.83,84
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