SEMINAR

Seminar

Oesophageal motility disorders

Joel E Richter

Oesophageal motility disorders comprise various abnormal manometric patterns which usually present with dysphagia
or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric
features, and good response to treatments directed at the pathophysiological abnormalities. Other disorders, such as
diffuse oesophageal spasm and hypercontracting oesophagus, have no well defined pathology and could represent a
range of motility changes associated with subtle neuropathic changes, gastro-oesophageal reflux, and anxiety states.
Although manometric patterns have been defined for these disorders, the relation with symptoms is poorly defined and
the response to medical or surgical therapy unpredictable. Hypocontracting oesophagus is generally caused by weak
musculature commonly associated with gastro-oesophageal reflux disease. Secondary oesophageal motility disorders
can be caused by collagen vascular diseases, diabetes, Chagas’ disease, amyloidosis, alcoholism, myxo-oedema,
multiple sclerosis, idiopathic pseudo-obstruction, or the ageing process.

The oesophageal motility disorders comprise any
condition whose symptoms, especially dysphagia and
chest pain, are suspected of being oesophageal in origin.
These disorders are diagnosed by oesophageal
manometry studies, which assess lower-oesophageal-
sphincter pressure and relaxation, the presence of
peristalsis in the oesophageal body, and the
characteristics of contraction waves including amplitude
(high or low), duration, repetitive nature, and presence
of either non-transmitted or partly transmitted waves.
Most assessments concentrate on the distal two-thirds of
the oesophagus, which consists of smooth muscle,
because pressure data and diseases in the proximal third
of the oesophagus (skeletal muscle) are less well
described and much less common. Normal values on
manometry studies have been calculated through the
study of large healthy populations, mainly by means of
pneumohydraulic water-perfusion systems.1,2 Although
authorities have proposed a number of classification
systems for the various abnormalities found by
manometry, none of them has been universally
accepted. Furthermore, there is much controversy over
the clinical importance of many of these abnormal
patterns, particularly as to whether they represent real
disorders or whether they are merely unusual findings
associated with a patient’s symptoms.3 This review will
focus on the following disorders outlined in panel 1:
achalasia, diffuse oesophageal spasm, hypercontracting
(nutcracker) oesophagus, hypocontracting oesophagus
(ineffective oesophageal motility), and secondary
oesophageal motility disorders.
Achalasia
Causes and pathological findings
Achalasia is the most recognised motor disorder of the
oesophagus and the only primary motility disorder with
an established pathology. The term means “failure to
relax”, and describes the predominant feature of this
disorder—a poorly relaxing lower oesophageal (cardiac)
Lancet 2001; 358: 823–28
Department of Gastroenterology, Cleveland Clinic Foundation,
Cleveland, OH 44195, USA (Prof J E Richter MD)
(e-mail: richtej@ccf.org)
sphincter. The first case of achalasia was reported more
than 300 years ago by Thomas Willis.4 The patient’s
cardiospasm responded to dilation with a whalebone.
The cause of achalasia is unknown. Available data
suggest that hereditary, degenerative, autoimmune, and
infectious factors are possible causes—the latter two
being the most commonly accepted.5 Pathological
changes identified at necropsy or from myotomy
Panel 1: Classification of primary oesophageal motility
disorders
Achalasia
Absent distal peristalsis
Abnormal lower-oesophageal-sphincter relaxation
Can have raised lower-oesophageal-sphincter pressure
(>45 mm Hg)
Diffuse oesophageal spasm
Simultaneous contractions ⭓20% of wet swallows
Intermittent peristalsis
Can have repetitive or multipeak contractions (⭓three peaks)
Can have spontaneous contractions not associated with
swallows
Contraction amplitude >30 mm Hg but usually not high
amplitude
Hypercontracting oesophagus
Hypertensive oesophagus—“nutcracker”
Increased mean distal amplitude (>180 mm Hg)
Normal peristalsis
Can be of increased distal duration (>6 s)
Hypertensive lower oesophageal sphincter
Resting lower oesophageal sphincter pressure >45 mm Hg
May be incomplete lower oesophageal sphincter relaxation
Hypocontracting oesophagus
Ineffective oesophageal motility
30% or more low distal amplitude (<30 mm Hg) or failed non-
transmitted contractions
Hypotensive lower oesophageal sphincter
Resting lower-oesophageal-sphincter pressure <10 mm Hg
Threshold values for lower oesophageal sphincter pressure and
contraction amplitude and duration based on studies on 95 healthy
adults.1 Values might vary in other laboratories, dependent on
equipment and techniques for measuring lower-oesophageal-sphincter
and oesophageal-body pressures.

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specimens are seen in the oesophageal myenteric
(Auerbach’s) plexus, and include a prominent but
patchy inflammatory response consisting of T
lymphocytes and variable numbers of eosinophils and
mast cells, loss of ganglion cells, and some degree of
myenteric neural fibrosis.6 The end result of these
inflammatory changes is a selective loss of post-
ganglionic inhibitory neurons containing nitric oxide
and vasoactive intestinal polypeptide. Since post-
ganglionic cholinergic neurons are spared, cholinergic
stimulation continues unopposed,7 leading to high basal
lower-oesophageal-sphincter pressures. The loss of
inhibitory input results in insufficient lower-
oesophageal-sphincter relaxation, and aperistalsis is
caused by loss of the latency gradient that permits
sequential contractions along the oesophageal body—a
process mediated by nitric oxide.
The diagnosis of achalasia should be suspected
in anyone with dysphagia for solids and liquids
with regurgitation of food and saliva.8 Patients
gradually learn to live with their dysphagia by using
various manoeuvres, including lifting the neck or
drinking carbonated beverages to help empty the
oesophagus. Regurgitation becomes a problem with
progression of the disease, especially when the
oesophagus begins to dilate. Regurgitation of bland,
undigested retained food or accumulated saliva occurs
most commonly in the recumbent position, waking the
patient from sleep because of coughing and choking.
Chest pain occurs in some patients, and is more
common in individuals with mild disease. Heartburn is a
frequent complaint of patients with achalasia, despite
the fact that achalasia is not associated with the reflux of
acidic gastric contents. The cause of this symptom is
speculative, but it is probably linked to the production
of lactic acid from retained food or to ingested acidic
material such as carbonated drinks. Most patients with
achalasia have some degree of weight loss at
presentation; however, the loss is usually slight, and
some patients are obese.
Symptoms and diagnosis
When achalasia is suspected, a barium swallow with
fluoroscopy should be done immediately.9 Early in the
disease, the oesophagus is normal in diameter, but with
a loss of normal peristalsis replaced by to-and-fro
movement in the supine position. As the disease
progresses, the oesophagus becomes more dilated and
tortuous, does not empty, and retained food and saliva
produce a heterogeneous air-fluid level at the top of the
barium column. The distal oesophagus is characterised
by a smooth tapering leading to the closed lower
oesophageal sphincter, resembling a bird’s beak. The
presence of an epiphrenic diverticulum in the distal
oesophagus suggests achalasia.10
Oesophageal manometry is the key test by which to
establish the diagnosis of achalasia,11 since a barium
swallow might not be sufficient, especially in the early
stages of the disease. Because achalasia involves the
smooth muscle portion of the oesophagus, the
manometric abnormalities are always confined to the
distal oesophagus. In the body of the oesophagus,
aperistalsis is always present, meaning that all wet or dry
swallows are followed by simultaneous contractions that
are identical to each other (isobaric or mirror images).
The contraction amplitudes are typically low
(10–40 mm Hg), and can be repetitive. The term
“vigorous achalasia” is sometimes used in the case
of aperistalsis with normal or even high amplitude
824
For personal use. Only reproduce with permission from The Lancet Publishing Group.
contractions in the oesophageal body.12 Some
manometric abnormality of the lower oesophageal
sphincter is always present in patients with achalasia.
The sphincter pressure is usually raised (never low), but
can be normal (10–45 mm Hg) in up to half of patients.
Abnormal lower-oesophageal-sphincter relaxation is
seen in all achalasia patients, and about 70–80% of
patients have absent or incomplete relaxation with wet
swallows. In the remaining 20–30%, the relaxations are
complete to the gastric baseline but are of short duration
(usually less than 6 s), and functionally inadequate, as
shown by barium and nuclear studies of emptying.13
Some tumours of the gastro-oesophageal junction can
produce pseudoachalasia. Therefore, all patients with
suspected achalasia should have an upper
gastrointestinal endoscopy with close examination of the
cardia and gastro-oesophageal junction. Endoscopic
ultrasonography and computed tomography scans are
sometimes needed to help make the diagnosis of
pseudoachalasia.
Treatment
No treatment can restore muscular activity to the
denervated oesophagus in achalasia. Oesophageal
aperistalsis and impaired lower oesophageal sphincter
relaxation are rarely, if ever, reversed by any mode of
therapy. Therefore, every treatment option for achalasia
is limited to reducing the pressure gradient across the
lower oesophageal sphincter, thus facilitating
oesophageal emptying by gravity and hopefully
preventing the further development of mega-
oesophagus.9 This pressure-gradient reduction can be
done most effectively by pneumatic dilation, surgical
myotomy, or, less effectively, by pharmacological agents
injected endoscopically into the lower oesophageal
sphincter (eg, botulinum toxin) or taken orally (eg,
calcium-channel blockers or nitrates).
Pneumatic dilation is the most effective non-surgical
treatment option for patients with achalasia.14 It involves
placing a balloon across the lower oesophageal
sphincter, which is then inflated to a pressure adequate
to tear the muscle fibres of the sphincter. The most
commonly used balloon dilators are the non-radiopaque
Rigiflex polyethylene balloons (Microvasive, Boston,
MA, USA), which come in three diameter sizes: 3·0,
3·5, and 4·0 cm. 50–93% of patients obtain good to
excellent relief of symptoms.14 The clinical response
improves proportionally with increasing balloon
diameter.15 The procedure can be done on an outpatient
basis, recovery is rapid, and discomfort is short-lived.
About 30% of patients might require subsequent
dilations. The main adverse event with pneumatic
dilation, which occurs at a cumulative rate of 2%, is
oesophageal perforation.14
Surgical myotomy for achalasia involves carrying out
an anterior myotomy across the lower oesophageal
sphincter (Heller’s myotomy). However, whether
myotomy should be combined with an antireflux
procedure (loose Nissen fundoplication, incomplete
Toupet, or Dor fundoplication) is a cause for debate.
Myotomies are usually done laparoscopically through
the abdomen with a 1–2 cm distal myotomy onto the
stomach.16 Good to excellent results are reported in
80–100% of patients.14 The major complication is
uncontrolled gastro-oesophageal reflux in about 10% of
patients.
Traditionally, symptom improvement is used to assess
the success of pneumatic dilation or surgical myotomy.
However, up to 30% of patients can feel better and still
THE LANCET • Vol 358 • September 8, 2001

Achalasia diagnosed
Low surgical High surgical risk/
risk unwilling to have
surgery
Laparoscopic Graded pneumatic Botulinum toxin
myotomy* dilation* (80–100 units)
Failure Success Failure Success Failure Success
Pneumatic Laparoscopic Repeat
dilation myotomy botulinum toxin
Failure Success Failure Success Failure Success
Oesophagectomy Nifedipine/isosorbide dinitrate
Suggested treatment algorithm for patients with achalasia
*Patients who are good surgical candidates should be given the option of
either graded pneumatic dilation or laparoscopic Heller myotomy. Those
who gain no benefit from the chosen surgical technique can be offered
the other.
have poor oesophageal emptying.17 Simple objective
testing such as follow-up manometry18 or a timed
barium swallow19 might help to define objective
improvement after treatment. Studies confirm that
patients with good oesophageal emptying have better
long-term symptom relief.20
Smooth-muscle relaxants including sublingual
isosorbide dinitrate or calcium blockers can be taken
prophylactically before meals or as necessary for pain or
dysphagia.21,22 These drugs provide variable relief of
symptoms, and their effectiveness tends to decrease with
time.14 Endoscopic injection of botulinum toxin type A
into the lower oesophageal sphincter is the most recent
treatment alternative for achalasia.23 Botulinum toxin
inhibits the calcium-dependent release of acetylcholine
from nerve terminals, thereby countering the effect of
the selective loss of inhibitory neurotransmitters. It is
initially effective in relieving symptoms in about 85% of
patients. However, symptoms recur in more than 50%
of these patients within 6 months, possibly because of
regeneration of the affected receptors.14 Additionally,
some reports indicate that myotomy might be more
difficult and less effective in patients previously treated
with botulinum toxin, possibly because of submucosal
scar formation at the site of injection.24 Older patients
(>60 years) and those with vigorous achalasia are more
likely to have a sustained response (up to 1·5 years) to
injection of botulinum toxin.25 The figure shows a
suggested treatment algorithm for patients with
achalasia.
Diffuse oesophageal spasm
Symptoms and cause
Diffuse oesophageal spasm is characterised by normal
peristalsis intermittently interrupted by simultaneous
contractions. The first description of oesophageal spasm
is attributed to Osgood, who, in 1889, described six
patients with severe chest pain and dysphagia with
meals.26 When accurately defined manometrically, the
THE LANCET • Vol 358 • September 8, 2001
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SEMINAR
disorder is quite rare, occurring in about 3–5% of
patients assessed for oesophageal motility disorders.27
The cause of diffuse oesophageal spasm is uncertain.
It is seen at any age, but most commonly in patients
older than 50 years; family clusters have been reported.
Evidence suggesting neural dysfunction has been seen
in some patients. Patients are hypersensitive to
cholinergic28 and hormonal (pentagastrin) stimulations,29
which generate abnormal oesophageal contractions and
sometimes chest pain. Occasionally, patients with
diffuse oesophageal spasm develop classic achalasia.
Other studies suggest that gastro-oesophageal reflux30
and stressful events31 can produce oesophageal spasm.
This enhanced oesophageal sensitivity might be
mediated by a defect in neural inhibition along the
oesophageal body, possibly in relation to decreased
available nitric oxide.32
Recurrent chest pain and dysphagia are the most
common presenting symptoms. Chest pain is variable in
frequency, intensity, and location, and commonly has a
pattern indistinguishable from that of cardiac angina,
including response to nitroglycerine. The pain can be
associated with meals and is rarely exertional. Dysphagia
is intermittent, non-progressive, and associated with
liquids and solids, and can be precipitated by stress,
liquids of extreme temperatures, or rapid eating. Many
patients also have symptoms compatible with irritable
bowel syndrome or urinary and sexual dysfunction in
women.33
Diagnosis
Diffuse oesophageal spasm is diagnosed by oesophageal
manometry showing intermittent simultaneous con-
tractions intermixed with normal peristalsis.34 On the
basis of studies of normal individuals, diffuse
oesophageal spasm is defined by the presence of
simultaneous contractions after 20% or more of wet
swallows.1,34,35 However, if all contractions are
simultaneous, the diagnosis is achalasia. Patients with
diffuse oesophageal spasm consist of two groups defined
by the amplitude of distal oesophageal contractions:
those with chest pain have high pressures, and those
with dysphagia have lower pressures.36 With the
recognition of the functional importance of low
amplitude ineffective contractions, simultaneous
contractions in diffuse oesophageal spasm should exceed
30 mm Hg. Other manometric findings less consistently
found include long-duration contractions, repetitive
waves (three peaks or more), spontaneous non-swallow-
induced contractions, and abnormalities of lower-
oesophageal sphincter-pressure or relaxation.34,37
The results of radiographic studies in diffuse
oesophageal spasm are variable. Many examinations are
normal, whereas others show disruption of peristalsis
with tertiary activity producing segmentation of the
oesophagus. Test results can vary from day to day, and
the amount of spastic activity does not correlate with
symptoms of chest pain.38 Provocative tests, such as
Tensilon28 or balloon distension,39 might be able to
induce the patient’s chest pain. Ambulatory 24 h pH
monitoring is useful in the identification of associated
gastro-oesophageal reflux disease, which is present in
20–50% of these patients.3
Treatment
Many patients with diffuse oesophageal spasm respond
well to confident reassurance that their chest pain is not
coming from the heart and has an oesophageal origin.40
Gastro-oesophageal reflux should be identified and
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Panel 2: Potential therapies for diffuse oesophageal
spasm and hypercontracting oesophagus
Reassurance
Treat underlying gastro-oesophageal reflux
Smooth-muscle relaxants
Nitroglycerin 0·4 mg sublingual
Isosorbide dinitrate 10–30 mg twice daily
Dicycloverine 10–20 mg four times daily
Calcium-channel blockers
Nifedipine 10–30 mg four times daily
Diltiazem 90 mg four times daily
Psychotropic drugs
Trazodone, 100–150 mg once daily
Imipramine 50 mg once daily
Botulinum toxin
Static bougie dilation
Pneumatic dilation
Oesophageal myotomy
aggressively treated.41 Otherwise, no single drug has
proven efficacy in the treatment of diffuse oesophageal
spasm (panel 2).42 Smooth-muscle relaxants, such as
long-acting nitrates,43 calcium-channel blockers,44 and
anticholinergics45 can decrease high-amplitude con-
tractions, but do not consistently relieve chest pain.
Antidepressant medications can reduce the amount of
discomfort experienced and the patient’s reaction to
pain, without changing the oesophageal motility
abnormality.46,47 Passive dilation of the oesophagus with
bougies is of no value,48 but pneumatic dilation,49 or
botulinum toxin50 helps some patients with diffuse
oesophageal spasm and abnormalities of lower-
oesophageal-sphincter relaxation who complain of
severe dysphagia with documented delays in
oesophageal emptying. A long surgical myotomy can
help some patients with chest pain,51 but aggressive
intervention must be used cautiously since symptoms
are frequently not relieved.
Hypercontracting oesophagus
Patients with oesophageal-contraction pressures of high
amplitude (two SD above the mean of a large group of
normal individuals) are described as having a
“nutcracker” oesophagus when the high pressure occurs
in the oesophageal body,52 and a hypertensive lower
oesophageal sphincter when resting lower-oesophageal-
sphincter pressures are raised.53 Apart from these
contractions of increased pressure, all other contractions
are peristaltic, although their duration can be longer than
normal. These two manometric findings often coexist,
suggesting that they might represent a syndrome of a
hypercontractile oesophagus.54 Since no pathological
equivalent has been found, the cause of hypercontracting
oesophagus is uncertain; however, some high-pressure
contractions could be secondary to exogenous factors
such as gastro-oesophageal reflux55 or stress.56
The main complaint in patients with a hyper-
contracting oesophagus is chest pain; dysphagia is
relatively uncommon. In fact, nutcracker oesophagus is
the most common motility disorder reported in these
patients, being seen in 27–48% of patients with chest
pain who undergo manometry.3 Nevertheless, the
precise relation between chest pain and hyper-
contracting oesophagus is still uncertain. Patients are
usually symptom-free when the diagnosis is established
by oesphageal manometry. Possibly, these contractions
826
For personal use. Only reproduce with permission from The Lancet Publishing Group.
are a marker for more severe motility disturbances
present during chest pain, but the results of prolonged
ambulatory monitoring suggest that this is infrequently
the case.30 Additionally, relief from chest pain does not
predictably correlate with amplitude reduction by either
pharmacotherapy or surgical myotomy.51,57 Although the
relation is not causal, the high prevalence of nutcracker
oesophagus in patients with non-cardiac chest pain is
unlikely to be simple coincidence. The association with
high stress and irritants to the oesophagus (eg, acid
reflux) suggests that these hypercontracting motility
abnormalities might represent an epiphenomenon rather
than a primary motility disorder.
By definition, all patients with hypercontracting
oesophagus have normal peristalsis, so barium
radiographs are usually normal. As shown in panel 1,
nutcracker oesophagus is characterised by mean distal
oesophageal peristaltic amplitudes exceeding 180 mm
Hg or mean distal duration greater than 6 s, and
hypertensive lower oesophageal sphincter is defined by a
resting sphincter pressure exceeding 45 mm Hg.
Treatment of these syndromes is similar to treatment of
diffuse oesophageal spasm, and results are just as
unpredictable.41
Hypocontracting oesophagus
Most patients who are diagnosed as having non-specific
oesophageal motility disorders have motility tracings
characterised by either low-amplitude (<30 mm Hg)
peristaltic or simultaneous contractions in the distal
oesophagus, or failed peristalsis in which the wave does
not traverse the entire length of the distal oesophagus.58
These abnormalities have been renamed “ineffective
oesophageal motility”.58 The concept of low-amplitude
waves being ineffective is supported by previous studies
that used simultaneous manometry and barium
videoradiography to show that contraction waves of less
than 30 mm Hg in amplitude, even if peristaltic, do not
effectively transport and clear a barium bolus from the
oesophagus.59 Most patients with ineffective oesophageal
motility have gastro-oesophageal reflux disease,58 often
associated with respiratory or ear, nose, and throat
complaints.60 A low pressure in the lower oesophageal
sphincter is commonly seen in patients with gastro-
oesphageal reflux, suggesting that the hypocontractile
oesophagus could be secondary to chronic acid damage
to the distal oesophagus. The lower-oesophageal-
sphincter hypotension might not be severe, however,
and studies suggest that the abnormal acid exposure in
these patients correlates better with the weak
oesophageal pump than with the resting lower-
oesophageal-sphincter pressure.
Dysphagia is usually mild in patients with ineffective
oesophageal motility: heartburn and acid regurgitation
are more common. Severe dysphagia suggests the
presence of an anatomical problem such as oesophagitis
or a peptic stricture. Treatment is directed at controlling
the acid reflux with H2-receptor antagonists or proton-
pump inhibitors. Unfortunately, no drug can reliably
increase peristaltic amplitude. Cisapride was the best
drug for this purpose, but it was withdrawn from the
market in USA, and its use was restricted in most other
countries because of its association with serious and
sometimes fatal cardiac arrhythmias.61
Secondary oesophageal motility
abnormalities
Patients with secondary disorders of oesophageal
motility have abnormal motility patterns secondary to a
THE LANCET • Vol 358 • September 8, 2001

multisystem disease. In scleroderma, for example,
motility abnormalities are found in about 80% of
patients.62 The underlying disease process is caused by
vascular obliteration and secondary fibrosis that affects
the oesophageal smooth muscle and its innervation.63
This process produces a low pressure in the lower
oesophageal sphincter (<10 mm Hg) and weak
ineffective distal motility; the proximal oesophagus and
upper oesophageal sphincter, which consist of skeletal
muscle, are usually spared. These patients commonly
have gastro-oesophageal reflux disease, up to 60% have
oesophagitis, and some have Barrett’s oesophagus.64
These manometric features are not peculiar to
scleroderma and can be found, although less frequently,
in patients with other connective-tissue diseases, such as
mixed connective-tissue disease, rheumatoid arthritis,
and systemic lupus erythematosus,65 as well as reflux
disease and other idiopathic forms of hypocontracting
oesophagus.
Chagas’ disease, which is caused by infection with the
parasite Trypanosoma cruzi, produces an achalasia-like
syndrome in the oesophagus. However, unlike patients
with classic achalasia, patients with Chagas’ disease
have other evidence of systemic disease including
cardiomyopathy, megacolon, and megaureter.66 Auto-
nomic neuropathy can result in abnormal motility in
most patients with insulin-dependent diabetes, and can
sometimes resemble diffuse oesophageal spasm.67
Amyloidosis,68 alcoholism,69 myxoedma,70 and multiple
sclerosis71 can all be accompanied by hypocontractions
in the distal oesophagus. Chronic idiopathic intestinal
pseudo-obstruction is almost always associated with
abnormal motility, particularly loss of peristalsis in the
distal oesophagus, which can sometimes mimic
achalasia.72 Whether the abnormal manometry
frequently associated with gastro-oesophageal reflux
disease is a primary process (possibly inherited), or
develops secondary to chronic acid injury is uncertain.
Despite the introduction of the term “presbyo-
oesophagus”,73 evidence that ageing alone effects the
oesophagus is scant. However, there is some evidence
that patients in their 80s and 90s can develop a decrease
in oesophageal amplitude and an increased frequency of
simultaneous, often repetitive, contractions.73,74
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THE LANCET • Vol 358 • September 8, 2001