Esophageal Spasm

Background

Broadly, esophageal spasm can be divided into two major variants that are distinct entities: (1) diffuse esophageal spasm and (2) hypertensive peristalsis.

Diffuse esophageal spasm is characterized by contractions that are of normal amplitude but are uncoordinated, simultaneous, or rapidly propagated (see image below).

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Barium swallow demonstrates diffuse uncoordinated contractions of the esophagus in a patient with diffuse esophageal spasm.

Hypertensive peristalsis, also known as nutcracker esophagus, is diagnosed when contractions proceed in a coordinated manner but the amplitude is excessive. Hypercontractile esophagus, also known as jackhammer esophagus, is an extreme phenotype of hypertensive contractions in which contractions are of very high amplitude, involving the majority of the esophagus, and whose duration occurs for a prolonged period with a jackhammer-type appearance on high-resolution manometry.

Symptoms can include dysphagia, regurgitation, and noncardiac chest pain. Because of the vague symptoms and difficulty in diagnosis, esophageal spasm is often underdiagnosed and therefore not adequately treated. In many patients, manometric and radiologic abnormalities may not correlate with symptom presentation.

Currently, high-resolution manometry is the best diagnostic modality. Treatment includes calcium channel blockers, botulinum toxin, nitrates, tricyclic antidepressants, sildenafil, dilatation, myotomy, and esophagectomy. Research is ongoing to determine the underlying causes to improve diagnostic capabilities and therapeutic regimens in the future.^[1]

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Pathophysiology

The etiology of esophageal spasm is unknown. Increased release of acetylcholine appears to be a factor (sensitive to cholinergic stimulation), but the triggering event is not known. Other theories include gastric reflux or a primary nerve or motor disorder. Body mass index (BMI) and total cholesterol may be highly predictive factors for esophageal body contractility, whereas BMI and glucose may be predictive factors for lower esophageal sphincter contractile function.^[2]

The oropharyngeal swallow with primary and secondary peristaltic contractions of the esophageal body usually transports solid and liquid food boluses from the mouth to the stomach within 10 seconds. Motor abnormalities may not be present with every swallow, so dysphagia may seem to wax and wane. Solid and liquid food dysphagia suggests a neuromuscular disorder, whereas solid food dysphagia only suggests a structural problem causing mechanical obstruction. Very hot or cold liquids, loud noises, and stress may exacerbate dysphagia from esophageal spasm by stimulating muscular contractions.

The connection between unexplained chest pain and esophageal spasm was first discovered by William Osler in 1892. Nutcracker esophagus was first diagnosed in the 1970s.^{[3, 4]}

The esophagus is composed of two layers of muscle, the inner circular and the outer longitudinal layers. The esophagus can be divided into three zones, each with separate yet integrated anatomy and physiology.

The function of the upper and lower esophageal sphincters is coordinated with the oropharynx, esophageal body, and stomach. Within the swallowing process, voluntary and involuntary control mechanisms act together. In the esophagus, the activity of the two types of muscle, striated (voluntary) and smooth (involuntary), is intimately coordinated. This distinction has functional significance because most esophageal motor abnormalities involve the smooth muscle portion.

A number of mechanisms for the initiation and control of esophageal motor activity are located at different levels within the central nervous system, as well as peripherally within the intramural nerves and muscles. This redundancy has implications for the operation of reserve mechanisms when a primary control mechanism is damaged or dysfunctional.

Esophageal zones

The upper zone is composed entirely of striated muscle. This zone initiates the contractions that propel the food bolus down the esophagus. The upper esophageal sphincter (UES), named the cricopharyngeus muscle, is located in the upper zone.

The middle zone is composed of striated and smooth muscle. The inner circular muscle layer and the outer longitudinal muscle layer work in conjunction to propel the food bolus down the esophagus.

The lower zone contains the lower esophageal sphincter (LES). This sphincter is a thickening of the smooth muscle that is contracted tonically to prevent reflux. At rest, the pressure in the LES is usually 15-25 mm Hg. For food to pass into the stomach, the LES relaxes at the appropriate time.

Upper esophageal sphincter

When functioning properly, the esophagus can detect the presence of a food bolus at the UES and then coordinate the progression of the food down the esophagus to the stomach. When this does not occur in a coordinated fashion, the patient can develop symptoms of esophageal spasm or oropharyngeal dysphagia.

The UES is contracted tonically. Manometric evaluation of the UES reveals constant spiking activity. As food is sensed at the UES, the laryngeal muscles contract to move the cricoid cartilage anteriorly. The tonic contraction of the UES is inhibited, opening the UES to allow the passage of food. The inner circular muscles and longitudinal muscles of the remainder of the upper zone then propel the food. To propel the food, the longitudinal muscles must contract, followed immediately by contraction of the circular muscles. At the end of the upper zone, the initial wave dies out as another wave starts, propelling the food down to the middle zone. The nucleus solitarius in the brainstem controls swallowing in the upper zone.

Esophageal middle zone

The middle zone propels the food bolus from the upper zone to the lower zone. This segment consists of two muscle layers, an inner circular layer and an outer longitudinal layer.

In the middle zone, the striated muscle transitions to the smooth, or involuntary, muscle. The wave propagates down the esophagus by coordinated contractions. Again, the longitudinal muscles must contract before the circular muscle contracts. Furthermore, the contraction of the muscles must proceed caudally in an organized manner. If the muscle contraction is not orderly, the food bolus cannot progress effectively.

Two forces propel the food from cephalad to caudad. First, gravity pulls the food caudally. Second, the organized contractions of the muscles propel the food caudally. If a myotomy is performed, the contractions will be ineffective. Only gravity propels the food caudally. Thus, patients who have had a myotomy can be more likely to report dysphagia.

Lower esophageal sphincter

The lower zone contains the LES. This is a condensation of the smooth muscles. Tonically, this muscle is contracted and must relax to allow food to pass. Failure of the LES to relax to allow a food bolus to pass is termed achalasia.

Diffuse esophageal spasms

Simplistically, diffuse esophageal spasms occur when the propagative waves do not progress correctly. Usually, several segments of the esophagus contract simultaneously, preventing the propagation of the food bolus. In addition, diffuse esophageal spasms can be characterized by rapid wave progression down the esophagus or distinguished by a nonperistaltic response to swallowing. The usual presentation is intermittent dysphagia with occasional chest pain. Myotomy, which is performed only in extreme cases, can relieve the uncoordinated contractions.^{[5, 6, 7, 8, 9]}

Nutcracker and jackhammer esophagus

Nutcracker and jackhammer esophagus occur when the amplitude of the contractions exceed 2 standard deviations from normal. The contractions proceed in an organized manner, propelling food down the esophagus. These patients present with chest pain more often than they present with dysphagia, as they experience less dysphagia than patients with diffuse esophageal spasm.

Because the progression of the contractions occurs normally, patients often do not benefit from a myotomy. Even though the increased amplitude of the contractions can be demonstrated using manometry, the symptoms often do not correlate with the manometrically documented contractions.

The symptoms of diffuse esophageal spasm, nutcracker esophagus, and jackhammer esophagus may overlap and can be distinguished only by a motility study.

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Epidemiology

United States statistics

The incidence of esophageal spasm is about 1 case in 100,000 population per year.^[4] The symptoms range from mild to severe. Patients with mild symptoms often do not seek medical attention. Because of the similarity of symptoms of reflux disease and esophageal spasm, many patients may be misdiagnosed with reflux. Furthermore, reflux and spasm can occur concomitantly.

International statistics

Because the symptoms are mild (or even absent) in many patients, the true incidence is not known.

Race-, sex-, and age-related statistics

Esophageal spasm seemingly is more common in whites, and it may be more common in women than in men. However, esophageal spasm is rare in children, and its incidence increases with age.

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Prognosis

Prognosis is moderate. Symptom scores improve over time (3 y or longer) in diffuse esophageal spasm and nutcracker esophagus. The mortality rate is minuscule, but the morbidity rate is high.

No treatment is effective in all patients. Some patients do not respond to any treatment. In most patients, symptoms are controllable with a combination of treatment modalities.

Mortality/morbidity

Mortality is very rare, but morbidity can be significant.

Morbidity arises from an inability to eat, secondary to the pain, and the subsequent decline in the nutritional status. The pain can be incapacitating, preventing normal activity and leading to considerable psychological challenges and impairment in the patient's quality of life. The chest pain can mimic cardiac, pulmonary, or rheumatological chest pain, instigating appropriate workup.

Primary esophageal motility disorders rarely progress and are not known to be fatal.

Complications

Potential problems are based on the therapy. All medications have possible adverse effects, and patients should be monitored.

Esophageal perforation can occur with esophageal dilatation, leading to admission to the hospital, time lost from work, and possible surgery.

Operative complications are the same as for any operation on the esophagus. Esophageal perforation can occur during myotomy. If a perforation of the mucosa occurs, the defect should be closed and the patient should have a contrast-swallowing test prior to resuming oral feeding. Vagal injury can occur during the dissection. Other postoperative complications include wound infection, atelectasis, pneumonia, and persistent air leak. Any complication associated with a thoracic operation or an esophageal operation can occur.

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Patient Education

Patients should be educated about the symptoms and treatment options for the disease. Patient involvement and education are crucial to the success of any treatment modality.

For patient education resources, see Botox Injections.

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History and Physical Examination

History

Esophageal spasm usually presents with the following intermittent symptoms:

• Noncardiac chest pain (< 10% of causes of noncardiac chest pain are due to diffuse esophageal spasm; the pain is usually retrosternal, frequently radiates to the back, and can be more severe than angina.)
• Globus (ie, the sensation that an object is trapped in the throat)
• Dysphagia, which is more consistent and reproducible during investigative studies, may be reported by one third to two thirds of subjects
• Regurgitation
• Heartburn (About 20% of patients report heartburn.)

A correlation between uncoordinated contractions and chest pain can be difficult to document, and, usually, a disparity exists between symptoms and the manometric findings.

Symptoms are usually intermittent and variable from day to day. They may last between minutes and hours.

Pain may be associated with eating quickly or drinking hot, cold, or carbonated beverages.

Anxiety and depression are common in these patients.

Patients with nutcracker esophagus or high-amplitude peristaltic contractions usually present with chest pain, as only 10% experience dysphagia.

Physical examination

Physical examination is typically not helpful for making a diagnosis but may provide clues to a systemic disease if this is the underlying cause of the patient's dysphagia.

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Laboratory Studies

Laboratory evaluation usually does not aid in the diagnosis if the patient's history and physical examination findings are unremarkable for other diseases mentioned in the differential diagnosis. All differentials mentioned can present with esophageal dysmotility.

The diagnostic modalities of choice are barium swallow and esophageal manometry.

Blood glucose and hemoglobin A1C levels should be checked to rule out diabetes. However, patients can have esophageal spasm and diabetes concomitantly.

The findings discovered by monitoring a patient's pH can demonstrate reflux, which can present with somewhat similar symptoms. In fact, gastroesophageal reflux is thought by some to trigger esophageal spasm.

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Imaging Studies

Barium swallow

Barium swallow or esophagram is the best imaging study to aid in the diagnosis of esophageal spasm by evaluating for nonpropulsive contractions in the esophagus.

Diffuse esophageal spasm has a characteristic appearance of multiple simultaneous contractions causing a corkscrew appearance with segmentation (see the image below).

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Barium swallow demonstrates diffuse uncoordinated contractions of the esophagus in a patient with diffuse esophageal spasm.

Unlike in diffuse esophageal spasm, the barium swallow findings for nutcracker esophagus are not specific and can present minimal findings.

CT scanning

Nino-Murcia and colleagues demonstrated thickening of the esophagus with CT scan studies in patients with esophageal spasm.^[10] Muscular hypertrophy has been documented in some patients with diffuse esophageal spasm and nutcracker esophagus. The hypertrophy of the muscle wall is the cause of the increased thickness that is observed on CT scan images. The normal thickness of the esophagus is less than 3 mm.

Many other disease processes, including malignancy, cause thickening of the esophagus that can be seen radiographically. Thus, thickening of the esophagus seen on CT scan images should prompt further workup. Even in patients with symptoms consistent with esophageal spasm, thickening seen on CT scan images should not be dismissed as muscular hypertrophy secondary to the esophageal spasms without further investigation.

Ultrasonography

Catheter-based high-frequency intraluminal ultrasound imaging assesses both the sensory function and the motor function of the esophagus.^[11]  This imaging modality may be useful to differentiate diffuse esophageal spasm, nutcracker esophagus, and achalasia.

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Other Tests

Manometry

Two relatively recent advances have revolutionized the performance of clinical esophageal manometry: practical high-resolution manometric (HRM) systems and the development of sophisticated algorithms to display the expanded manometric dataset as esophageal pressure topographic plots.^{[12, 13]}

Two strengths of esophageal pressure topographic plots compared with conventional manometric recordings are the ability to delineate the spatial limits, vigor, and integrity of individual contractile segments along the esophagus and to distinguish between loci of the compartmentalized intraesophageal pressurization and rapidly propagated contractions.^[12] See the image below.

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High-resolution manometric display of a normal esophageal swallow using esophageal pressure topography. Image courtesy of Wikimedia Commons.

Manometry is the best modality to help diagnose diffuse esophageal spasm as well as esophageal spasm as the cause of noncardiac chest pain.^[14] Findings include aperistalsis in greater than 30% of the wet swallows, 20% of contractions being simultaneous, amplitudes greater than 30 mm Hg in the distal three fifths of the esophagus, and, rarely, repetitive contractions or lower esophageal sphincter (LES) dysfunction. Vigorous achalasia can easily be confused with diffuse esophageal spasm.^[4]

Diffuse esophageal spasm, when defined by premature contractions measured with distal latency, describes a more clinically homogeneous entity than when defined by contractile front velocity.^[15]

The classic definition is more than 2 uncoordinated contractions during 10 consecutive wet swallows (≥20% simultaneous esophageal contractions during standardized stationary motility testing). At least one peristaltic contraction must be present. Artificial neural networks may be useful in the recognition and objective classification of primary esophageal motor disorders investigated with stationary esophageal manometry recordings.^[16]

Herbella et al conducted a study in patients with manometric patterns of diffuse esophageal spasm and nutcracker esophagus to determine whether symptoms alone can distinguish primary esophageal motility disorder from gastroesophageal reflux disease, a secondary esophageal motility disorder, and the value of ambulatory pH monitoring.^[17] Of  the 180 patients with manometric criteria for nutcracker esophagus, 124 (69%) had gastroesophageal reflux that was detected with ambulatory pH monitoring. Of the 56 patients with primary esophageal motility disorder, 31 (55%) were taking proton pump inhibitors.^[17] No difference in chest pain prevalence was noted between the groups, but those with primary esophageal motility disorder had greater chest pain symptom severity, whereas patients in the gastroesophageal reflux group had a higher prevalence and severity of heartburn.^[17]

Of the 121 patients with manometric criteria for diffuse esophageal spasm, 73 (60%) demonstrated gastroesophageal reflux by ambulatory pH monitoring.^[17] Of the 48 patients with primary esophageal motility disorder, 39 (81%) were on proton pump inhibitors. The group with primary esophageal motility had a higher prevalence of dysphagia disorder relative to the gastroesophageal reflux group.

Herbella et al thus demonstrated that two thirds of patients with a manometric pattern of diffuse esophageal spasm or nutcracker esophagus also had gastroesophageal reflux disease, and the symptoms were indistinguishable between primary esophageal motility disorders and gastroesophageal reflux disease. They concluded that esophageal manometry and pH monitoring are crucial to distinguish between primary and secondary esophageal motility disorders and to guide appropriate therapy.^[17]

Contraction amplitude is normal.

The distal contractile integral (DCI) is the metric used to define the vigor of the contraction. It is the product of the amplitude, duration, and length of the contraction between the proximal and distal trough.

Nutcracker esophagus is defined as a mean DCI greater than 5000 mm Hg/s/cm over 10 swallows using esophageal pressure topography criteria. This occurs in the context of normal propagation and normal esophagogastric junction relaxation.

Jackhammer esophagus is an extreme phenotype of hypertensive contraction characterized by a DCI greater than 8000 mm Hg/s/cm. This phenotype is never found in asymptomatic patients.^[18]

The image below depicts a normal manometric tracing. This depiction uses the older system of pressure tracings (conventional manometric recording) without high-resolution esophageal pressure topography.

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This is normal esophageal manometry tracing with normal amplitude of the contractions. The contractions are coordinated because the contractions in th....

The image below depicts an example of diffuse esophageal spasm.

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Esophageal manometry tracing demonstrates diffuse esophageal spasm. Note the multiple uncoordinated contractions in the third tracing from the distal ....

Manometry in patients with nutcracker esophagus demonstrates contractions that progress in an orderly manner, but the amplitude of the contraction is excessive. Amplitude greater than 2 standard deviations above the normal value is considered diagnostic for nutcracker esophagus (see the image below).

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Esophageal manometry tracing demonstrates nutcracker esophagus. Note the excessive amplitude of the contractions.

A disassociation may exist between symptoms and the manometric findings.

Esophageal electrical impedance recordings show abnormal transit in diffuse esophageal spasm.

Esophageal manometry may be combined with multichannel intraluminal impedance to obtain pressure and bolus transit information.^{[19, 20]} About half of the patients with diffuse esophageal spasm have normal transit for liquids and fluids, one fourth have abnormal transit for one substance, and one fourth have abnormal transit for both.

Esophageal pH recording and 24-hour ambulatory manometry may improve the detection of esophageal muscle dysfunction.^[21] This method shows that in persons presenting with noncardiac chest pain, gastroesophageal reflux symptoms are common and diffuse esophageal spasm is rare.

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Procedures

Esophagogastroduodenoscopy (EGD), or upper endoscopy, can reveal associated disorders such as hiatal hernia, reflux esophagitis, and strictures.

Endoscopy is not useful to help diagnose dysmotility, but it may be helpful to exclude erosive esophagitis or stricture.

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Approach Considerations

Usually, the workup and treatment are performed in an outpatient setting. Patients in whom medical management fails and who require operative intervention should have routine postoperative care based on the procedure performed.

Calcium channel blockers and nitrates are first-line therapy.

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Medical Care

Sildenafil, a phosphodiesterase inhibitor, is a smooth muscle relaxant that can lower the LES pressure and spastic contractions of the esophagus in nutcracker esophagus.

Botulinum toxin binds receptors in the nerve endings, thereby decreasing the release of acetylcholine. By endoscopically injecting botulinum toxin above the LES, symptoms may improve.^[22] The effect is temporary, and the response decreases with repeated injections.

Balloon dilatation is commonly used for achalasia, but it has been also used to treat diffuse esophageal spasm and nutcracker esophagus.^[23] The studies are small, the relief is not uniform, and symptoms recur. Dilation with mercury-filled bougies has been used in the past.^[24]

Proton pump inhibitors effectively reduce or alleviate the symptoms of gastroesophageal reflux disease, which may mimic diffuse esophageal spasm.^[25] A trial of acid-lowering therapy may be undertaken prior to instituting other treatments. Although treatment is often ineffective, the symptoms from diffuse esophageal spasm and nutcracker esophagus usually improve over time.

Tricyclic antidepressants have produced much success in the treatment of many patients with esophageal motility disorders. Some of these patients may have associated psychiatric illnesses, and concomitant treatment of those conditions may improve outcomes.

Diet

Diet-induced symptoms are patient-specific. Dietary restriction, even to pureed foods, can decrease symptoms temporarily.

Outpatient monitoring

Patients need close follow-up care upon the initiation of therapy or with a change in therapy. Patients should be monitored for improvements in symptoms and for adverse effects of the medications.

Patients in whom medical management fails should be referred to a thoracic surgeon for possible operative intervention.

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Surgical Care

For extreme cases, operative treatment usually involves a myotomy. Myotomy relieves symptoms by eliminating the effectiveness of the contractions. Traditionally, a thoracotomy was required to obtain access to the esophagus, but now, a thoracoscopic approach can be used. In rare, recalcitrant cases, esophagectomy can relieve symptoms.

Myotomy is effective for treating diffuse esophageal spasm.^[26] The myotomy should extend the entire length of the involved segment, which should be determined preoperatively with manometry. Furthermore, the myotomy should extend through the lower esophageal sphincter (LES) to help prevent dysphagia postoperatively by preventing outlet obstruction. Finally, an antireflux procedure should be performed concomitantly, by either a partial wrap or a Nissen fundoplication.

Myotomy should be used with caution in patients with nutcracker esophagus because it may worsen the symptoms. Myotomy reduces the amplitude of the contractions, but this does not consistently improve symptoms, especially if the primary complaint is pain. Furthermore, dysphagia can develop or worsen after myotomy because the effectiveness of the propagative waves is eliminated, leaving gravity to propel food caudally.

As a last resort, esophagectomy can be used to relieve symptoms. The esophagus is resected, and the stomach, small intestine, or colon is used to restore the continuity of the GI tract. Morbidity and mortality of esophagectomy are substantial; therefore, this procedure should be performed only after other treatments have been exhausted.

Overall, surgical therapy is reserved for those refractory to medical therapy. Filicori et al concluded that chest pain and dysphagia can be effectively palliated with per oral endoscopic myotomy (POEM) in patients with non-achalasia disorders of the esophagus.^[27]

A thoracoscopy with a long myotomy from the arch of the aorta across the LES with an antireflux surgery is a commonly performed procedure in this setting.

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Medication Summary

Medical therapy is the first line of treatment for esophageal spasm. Because the etiology is unknown, all medical therapies are directed at symptoms, not the etiology. Proton pump inhibitors may be useful for associated gastroesophageal reflux disease. Calcium channel blockers and nitrates may decrease pain associated with esophageal spasms. Botulinum toxin decreases acetylcholine available at nerve endings. Imipramine improves pain by an unknown mechanism of action.

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Diltiazem (Cardizem, Cartia XT, Dilacor XR, Diltzac, Tiazac, Diltia XT)

• Dosing, Interactions, etc.

Clinical Context:  Diltiazem is FDA approved for hypertension, vasospastic angina, and chronic stable angina. It decreases calcium ion flux across cell membranes in smooth muscle, thereby relaxing the vascular smooth muscle.

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Class Summary

Calcium channel blockers reduce the amplitude of contractions. In nutcracker esophagus, calcium channel blockers effectively reduce the amplitude of contractions, but chest pain often is not reduced. Whether calcium channel blockers decrease the force of contraction of muscle or decrease the underlying stimulus is unknown.

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Isosorbide dinitrate (Dilatate SR, Isordil, Isoditrate ER)

• Dosing, Interactions, etc.

Clinical Context:  The approved indication is for angina pectoris. Isosorbide dinitrate relaxes vascular smooth muscle by stimulating the intracellular cyclic GMP. By decreasing left ventricular pressure and dilating the arteries, it reduces cardiac oxygen demand.

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Class Summary

Like calcium channel blockers, nitrates may decrease the pain associated with esophageal spasm. The mechanism of action is unknown, but it may be related to decreasing vasospasm in the brainstem, similar to calcium channel blockers, or it may be due to a direct effect on the myocytes.

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Imipramine (Tofranil, Tofranil PM)

• Dosing, Interactions, etc.

Clinical Context:  Imipramine decreases pain in patients with chest pain of no apparent cause on angiography, which may be esophageal spasm. This is not an FDA-approved use. The mechanism of action is not known. The primary use of imipramine is in the treatment of depression.

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Class Summary

These agents, specifically imipramine, have been shown to decrease chest pain of no apparent cause on angiography. Studies specifically evaluating nutcracker esophagus are not yet available. The mechanism of action of imipramine is not known.

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Botulinum toxin (BOTOX®)

• Dosing, Interactions, etc.

Clinical Context:  Botulinum toxin treats excessive abnormal contractions associated with blepharospasm. It binds to receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which, in turn, inhibits the transmission of impulses in neuromuscular tissue.

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Class Summary

This class binds receptors in nerve endings, decreasing the release of acetylcholine. Injecting botulinum toxin endoscopically above the lower esophageal sphincter (LES) improves the symptoms of patients with esophageal spasms. However, the effect is temporary and the response decreases with repeated injections.

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Sildenafil (Revation, Viagra)

• Dosing, Interactions, etc.

Clinical Context:  Sildenafil acts by inhibiting cGMP-specific phosphodiesterase type 5, an enzyme that promotes the degradation of cGMP, thereby enhancing the effects of nitric oxide-activated increases in cGMP, resulting in smooth muscle relaxation.

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Class Summary

These agents can relax smooth muscle.

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