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

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SEMINAR

specimens are seen in the oesophageal myenteric contractions in the oesophageal body.12 Some
(Auerbach’s) plexus, and include a prominent but manometric abnormality of the lower oesophageal
patchy inflammatory response consisting of T sphincter is always present in patients with achalasia.
lymphocytes and variable numbers of eosinophils and The sphincter pressure is usually raised (never low), but
mast cells, loss of ganglion cells, and some degree of can be normal (10–45 mm Hg) in up to half of patients.
myenteric neural fibrosis.6 The end result of these Abnormal lower-oesophageal-sphincter relaxation is
inflammatory changes is a selective loss of post- seen in all achalasia patients, and about 70–80% of
ganglionic inhibitory neurons containing nitric oxide patients have absent or incomplete relaxation with wet
and vasoactive intestinal polypeptide. Since post- swallows. In the remaining 20–30%, the relaxations are
ganglionic cholinergic neurons are spared, cholinergic complete to the gastric baseline but are of short duration
stimulation continues unopposed,7 leading to high basal (usually less than 6 s), and functionally inadequate, as
lower-oesophageal-sphincter pressures. The loss of shown by barium and nuclear studies of emptying.13
inhibitory input results in insufficient lower- Some tumours of the gastro-oesophageal junction can
oesophageal-sphincter relaxation, and aperistalsis is produce pseudoachalasia. Therefore, all patients with
caused by loss of the latency gradient that permits suspected achalasia should have an upper
sequential contractions along the oesophageal body—a gastrointestinal endoscopy with close examination of the
process mediated by nitric oxide. cardia and gastro-oesophageal junction. Endoscopic
The diagnosis of achalasia should be suspected ultrasonography and computed tomography scans are
in anyone with dysphagia for solids and liquids sometimes needed to help make the diagnosis of
with regurgitation of food and saliva.8 Patients pseudoachalasia.
gradually learn to live with their dysphagia by using
various manoeuvres, including lifting the neck or Treatment
drinking carbonated beverages to help empty the No treatment can restore muscular activity to the
oesophagus. Regurgitation becomes a problem with denervated oesophagus in achalasia. Oesophageal
progression of the disease, especially when the aperistalsis and impaired lower oesophageal sphincter
oesophagus begins to dilate. Regurgitation of bland, relaxation are rarely, if ever, reversed by any mode of
undigested retained food or accumulated saliva occurs therapy. Therefore, every treatment option for achalasia
most commonly in the recumbent position, waking the is limited to reducing the pressure gradient across the
patient from sleep because of coughing and choking. lower oesophageal sphincter, thus facilitating
Chest pain occurs in some patients, and is more oesophageal emptying by gravity and hopefully
common in individuals with mild disease. Heartburn is a preventing the further development of mega-
frequent complaint of patients with achalasia, despite oesophagus.9 This pressure-gradient reduction can be
the fact that achalasia is not associated with the reflux of done most effectively by pneumatic dilation, surgical
acidic gastric contents. The cause of this symptom is myotomy, or, less effectively, by pharmacological agents
speculative, but it is probably linked to the production injected endoscopically into the lower oesophageal
of lactic acid from retained food or to ingested acidic sphincter (eg, botulinum toxin) or taken orally (eg,
material such as carbonated drinks. Most patients with calcium-channel blockers or nitrates).
achalasia have some degree of weight loss at Pneumatic dilation is the most effective non-surgical
presentation; however, the loss is usually slight, and treatment option for patients with achalasia.14 It involves
some patients are obese. placing a balloon across the lower oesophageal
sphincter, which is then inflated to a pressure adequate
Symptoms and diagnosis to tear the muscle fibres of the sphincter. The most
When achalasia is suspected, a barium swallow with commonly used balloon dilators are the non-radiopaque
fluoroscopy should be done immediately.9 Early in the Rigiflex polyethylene balloons (Microvasive, Boston,
disease, the oesophagus is normal in diameter, but with MA, USA), which come in three diameter sizes: 3·0,
a loss of normal peristalsis replaced by to-and-fro 3·5, and 4·0 cm. 50–93% of patients obtain good to
movement in the supine position. As the disease excellent relief of symptoms.14 The clinical response
progresses, the oesophagus becomes more dilated and improves proportionally with increasing balloon
tortuous, does not empty, and retained food and saliva diameter.15 The procedure can be done on an outpatient
produce a heterogeneous air-fluid level at the top of the basis, recovery is rapid, and discomfort is short-lived.
barium column. The distal oesophagus is characterised About 30% of patients might require subsequent
by a smooth tapering leading to the closed lower dilations. The main adverse event with pneumatic
oesophageal sphincter, resembling a bird’s beak. The dilation, which occurs at a cumulative rate of 2%, is
presence of an epiphrenic diverticulum in the distal oesophageal perforation.14
oesophagus suggests achalasia.10 Surgical myotomy for achalasia involves carrying out
Oesophageal manometry is the key test by which to an anterior myotomy across the lower oesophageal
establish the diagnosis of achalasia,11 since a barium sphincter (Heller’s myotomy). However, whether
swallow might not be sufficient, especially in the early myotomy should be combined with an antireflux
stages of the disease. Because achalasia involves the procedure (loose Nissen fundoplication, incomplete
smooth muscle portion of the oesophagus, the Toupet, or Dor fundoplication) is a cause for debate.
manometric abnormalities are always confined to the Myotomies are usually done laparoscopically through
distal oesophagus. In the body of the oesophagus, the abdomen with a 1–2 cm distal myotomy onto the
aperistalsis is always present, meaning that all wet or dry stomach.16 Good to excellent results are reported in
swallows are followed by simultaneous contractions that 80–100% of patients.14 The major complication is
are identical to each other (isobaric or mirror images). uncontrolled gastro-oesophageal reflux in about 10% of
The contraction amplitudes are typically low patients.
(10–40 mm Hg), and can be repetitive. The term Traditionally, symptom improvement is used to assess
“vigorous achalasia” is sometimes used in the case the success of pneumatic dilation or surgical myotomy.
of aperistalsis with normal or even high amplitude However, up to 30% of patients can feel better and still

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 SEMINAR

Achalasia diagnosed
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
Low surgical High surgical risk/
risk unwilling to have
older than 50 years; family clusters have been reported.
surgery Evidence suggesting neural dysfunction has been seen
in some patients. Patients are hypersensitive to
cholinergic28 and hormonal (pentagastrin) stimulations,29
Laparoscopic Graded pneumatic Botulinum toxin
myotomy* dilation* (80–100 units)
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
Failure Success Failure Success Failure Success
and stressful events31 can produce oesophageal spasm.
This enhanced oesophageal sensitivity might be
mediated by a defect in neural inhibition along the
Pneumatic Laparoscopic Repeat oesophageal body, possibly in relation to decreased
dilation myotomy botulinum toxin available nitric oxide.32
Recurrent chest pain and dysphagia are the most
common presenting symptoms. Chest pain is variable in
Failure Success Failure Success Failure Success frequency, intensity, and location, and commonly has a
pattern indistinguishable from that of cardiac angina,
including response to nitroglycerine. The pain can be
Oesophagectomy Nifedipine/isosorbide dinitrate associated with meals and is rarely exertional. Dysphagia
is intermittent, non-progressive, and associated with
liquids and solids, and can be precipitated by stress,
Suggested treatment algorithm for patients with achalasia liquids of extreme temperatures, or rapid eating. Many
*Patients who are good surgical candidates should be given the option of patients also have symptoms compatible with irritable
either graded pneumatic dilation or laparoscopic Heller myotomy. Those bowel syndrome or urinary and sexual dysfunction in
who gain no benefit from the chosen surgical technique can be offered
the other. women.33

have poor oesophageal emptying.17 Simple objective Diagnosis

testing such as follow-up manometry18 or a timed Diffuse oesophageal spasm is diagnosed by oesophageal
barium swallow19 might help to define objective manometry showing intermittent simultaneous con-
improvement after treatment. Studies confirm that tractions intermixed with normal peristalsis.34 On the
patients with good oesophageal emptying have better basis of studies of normal individuals, diffuse
long-term symptom relief.20 oesophageal spasm is defined by the presence of
Smooth-muscle relaxants including sublingual simultaneous contractions after 20% or more of wet
isosorbide dinitrate or calcium blockers can be taken swallows.1,34,35 However, if all contractions are
prophylactically before meals or as necessary for pain or simultaneous, the diagnosis is achalasia. Patients with
dysphagia.21,22 These drugs provide variable relief of diffuse oesophageal spasm consist of two groups defined
symptoms, and their effectiveness tends to decrease with by the amplitude of distal oesophageal contractions:
time.14 Endoscopic injection of botulinum toxin type A those with chest pain have high pressures, and those
into the lower oesophageal sphincter is the most recent with dysphagia have lower pressures.36 With the
treatment alternative for achalasia.23 Botulinum toxin recognition of the functional importance of low
inhibits the calcium-dependent release of acetylcholine amplitude ineffective contractions, simultaneous
from nerve terminals, thereby countering the effect of contractions in diffuse oesophageal spasm should exceed
the selective loss of inhibitory neurotransmitters. It is 30 mm Hg. Other manometric findings less consistently
initially effective in relieving symptoms in about 85% of found include long-duration contractions, repetitive
patients. However, symptoms recur in more than 50% waves (three peaks or more), spontaneous non-swallow-
of these patients within 6 months, possibly because of induced contractions, and abnormalities of lower-
regeneration of the affected receptors.14 Additionally, oesophageal sphincter-pressure or relaxation.34,37
some reports indicate that myotomy might be more The results of radiographic studies in diffuse
difficult and less effective in patients previously treated oesophageal spasm are variable. Many examinations are
with botulinum toxin, possibly because of submucosal normal, whereas others show disruption of peristalsis
scar formation at the site of injection.24 Older patients with tertiary activity producing segmentation of the
(>60 years) and those with vigorous achalasia are more oesophagus. Test results can vary from day to day, and
likely to have a sustained response (up to 1·5 years) to the amount of spastic activity does not correlate with
injection of botulinum toxin.25 The figure shows a symptoms of chest pain.38 Provocative tests, such as
suggested treatment algorithm for patients with Tensilon28 or balloon distension,39 might be able to
achalasia. induce the patient’s chest pain. Ambulatory 24 h pH
monitoring is useful in the identification of associated
Diffuse oesophageal spasm gastro-oesophageal reflux disease, which is present in
Symptoms and cause 20–50% of these patients.3
Diffuse oesophageal spasm is characterised by normal
peristalsis intermittently interrupted by simultaneous Treatment
contractions. The first description of oesophageal spasm Many patients with diffuse oesophageal spasm respond
is attributed to Osgood, who, in 1889, described six well to confident reassurance that their chest pain is not
patients with severe chest pain and dysphagia with coming from the heart and has an oesophageal origin.40
meals.26 When accurately defined manometrically, the Gastro-oesophageal reflux should be identified and

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SEMINAR

Panel 2: Potential therapies for diffuse oesophageal are a marker for more severe motility disturbances
spasm and hypercontracting oesophagus present during chest pain, but the results of prolonged
ambulatory monitoring suggest that this is infrequently
Reassurance the case.30 Additionally, relief from chest pain does not
Treat underlying gastro-oesophageal reflux predictably correlate with amplitude reduction by either
Smooth-muscle relaxants pharmacotherapy or surgical myotomy.51,57 Although the
Nitroglycerin 0·4 mg sublingual relation is not causal, the high prevalence of nutcracker
Isosorbide dinitrate 10–30 mg twice daily oesophagus in patients with non-cardiac chest pain is
Dicycloverine 10–20 mg four times daily unlikely to be simple coincidence. The association with
high stress and irritants to the oesophagus (eg, acid
Calcium-channel blockers
reflux) suggests that these hypercontracting motility
Nifedipine 10–30 mg four times daily
abnormalities might represent an epiphenomenon rather
Diltiazem 90 mg four times daily
than a primary motility disorder.
Psychotropic drugs By definition, all patients with hypercontracting
Trazodone, 100–150 mg once daily oesophagus have normal peristalsis, so barium
Imipramine 50 mg once daily radiographs are usually normal. As shown in panel 1,
Botulinum toxin nutcracker oesophagus is characterised by mean distal
Static bougie dilation oesophageal peristaltic amplitudes exceeding 180 mm
Hg or mean distal duration greater than 6 s, and
Pneumatic dilation hypertensive lower oesophageal sphincter is defined by a
Oesophageal myotomy resting sphincter pressure exceeding 45 mm Hg.
Treatment of these syndromes is similar to treatment of
aggressively treated.41 Otherwise, no single drug has diffuse oesophageal spasm, and results are just as
proven efficacy in the treatment of diffuse oesophageal unpredictable.41
spasm (panel 2).42 Smooth-muscle relaxants, such as
long-acting nitrates,43 calcium-channel blockers,44 and Hypocontracting oesophagus
anticholinergics45 can decrease high-amplitude con- Most patients who are diagnosed as having non-specific
tractions, but do not consistently relieve chest pain. oesophageal motility disorders have motility tracings
Antidepressant medications can reduce the amount of characterised by either low-amplitude (<30 mm Hg)
discomfort experienced and the patient’s reaction to peristaltic or simultaneous contractions in the distal
pain, without changing the oesophageal motility oesophagus, or failed peristalsis in which the wave does
abnormality.46,47 Passive dilation of the oesophagus with not traverse the entire length of the distal oesophagus.58
bougies is of no value,48 but pneumatic dilation,49 or These abnormalities have been renamed “ineffective
botulinum toxin50 helps some patients with diffuse oesophageal motility”.58 The concept of low-amplitude
oesophageal spasm and abnormalities of lower- waves being ineffective is supported by previous studies
oesophageal-sphincter relaxation who complain of that used simultaneous manometry and barium
severe dysphagia with documented delays in videoradiography to show that contraction waves of less
oesophageal emptying. A long surgical myotomy can than 30 mm Hg in amplitude, even if peristaltic, do not
help some patients with chest pain,51 but aggressive effectively transport and clear a barium bolus from the
intervention must be used cautiously since symptoms oesophagus.59 Most patients with ineffective oesophageal
are frequently not relieved. motility have gastro-oesophageal reflux disease,58 often
associated with respiratory or ear, nose, and throat
Hypercontracting oesophagus complaints.60 A low pressure in the lower oesophageal
Patients with oesophageal-contraction pressures of high sphincter is commonly seen in patients with gastro-
amplitude (two SD above the mean of a large group of oesphageal reflux, suggesting that the hypocontractile
normal individuals) are described as having a oesophagus could be secondary to chronic acid damage
“nutcracker” oesophagus when the high pressure occurs to the distal oesophagus. The lower-oesophageal-
in the oesophageal body,52 and a hypertensive lower sphincter hypotension might not be severe, however,
oesophageal sphincter when resting lower-oesophageal- and studies suggest that the abnormal acid exposure in
sphincter pressures are raised.53 Apart from these these patients correlates better with the weak
contractions of increased pressure, all other contractions oesophageal pump than with the resting lower-
are peristaltic, although their duration can be longer than oesophageal-sphincter pressure.
normal. These two manometric findings often coexist, Dysphagia is usually mild in patients with ineffective
suggesting that they might represent a syndrome of a oesophageal motility: heartburn and acid regurgitation
hypercontractile oesophagus.54 Since no pathological are more common. Severe dysphagia suggests the
equivalent has been found, the cause of hypercontracting presence of an anatomical problem such as oesophagitis
oesophagus is uncertain; however, some high-pressure or a peptic stricture. Treatment is directed at controlling
contractions could be secondary to exogenous factors the acid reflux with H2-receptor antagonists or proton-
such as gastro-oesophageal reflux55 or stress.56 pump inhibitors. Unfortunately, no drug can reliably
The main complaint in patients with a hyper- increase peristaltic amplitude. Cisapride was the best
contracting oesophagus is chest pain; dysphagia is drug for this purpose, but it was withdrawn from the
relatively uncommon. In fact, nutcracker oesophagus is market in USA, and its use was restricted in most other
the most common motility disorder reported in these countries because of its association with serious and
patients, being seen in 27–48% of patients with chest sometimes fatal cardiac arrhythmias.61
pain who undergo manometry.3 Nevertheless, the
precise relation between chest pain and hyper- Secondary oesophageal motility
contracting oesophagus is still uncertain. Patients are abnormalities
usually symptom-free when the diagnosis is established Patients with secondary disorders of oesophageal
by oesphageal manometry. Possibly, these contractions motility have abnormal motility patterns secondary to a

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 SEMINAR

multisystem disease. In scleroderma, for example, lower esophageal diverticulum and its complications for treatment.
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