Background

Broadly, esophageal spasm can be subdivided into 2 distinct entities: (1) diffuse esophageal spasm (DES), in which contractions are uncoordinated, and (2) nutcracker esophagus, in which contractions proceed in a coordinated manner, but the amplitude is excessive. Symptoms can include dysphagia, regurgitation, and noncardiac chest pain. Because of the vague symptoms and difficulty in diagnosis, esophageal spasm often is not diagnosed and is undertreated. Many patients with manometric and radiologic aberrations may not have any appreciable symptoms. Currently, manometry is the best diagnostic modality. Treatment includes calcium channel blockers, botulinum toxin, nitrates, tricyclic antidepressants, dilatation, myotomy, and esophagectomy. Research is ongoing to unlock the underlying causes to improve our diagnostic capabilities and therapeutic regimens in the future.

Pathophysiology
The esophagus is comprised of 2 layers of muscle, the inner circular and the outer longitudinal layers. Arbitrarily, the esophagus can be divided into 3 zones, each with separate yet integrated anatomy and physiology. Esophageal zones Upper zone: Comprised 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. Middle zone: Comprised of striated and smooth muscles, the inner circular muscle layer and the outer longitudinal muscle layer work in conjunction to propel the food bolus. Lower zone: The lower segment is 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.

Upper esophageal sphincter When functioning properly, the esophagus can detect the presence of a food bolus at the UES and then coordinate 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. 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 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 2 muscle layers, an inner circular and outerlongitudinal layer. In the middle zone, the striated muscle transitions to 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, contraction of the muscles must proceed caudally in an organized manner. If the muscle contraction is not orderly, the food bolus cannot progress. Two forces propel the food from cephalad to caudad. First, gravity pulls the food caudally. The organized contractions of the muscles propel the food caudally. If a myotomy is performed, the contractions will be ineffective. Only gravity forces the food caudally. Thus, patients who have had a myotomy are more likely to have dysphagia. Lower esophageal sphincter The lower zone is comprised of 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 (see Achalasia). Diffuse esophageal spasms Simplistically, DESs occur when the propagative waves do not progress correctly. Usually, several segments of the esophagus contract simultaneously, preventing the propagation of the food bolus. The usual presentation is intermittent dysphagia with occasional chest pain. Myotomy, which is performed only in extreme cases, can relieve the uncoordinated contractions. Nutcracker esophagus Nutcracker esophagus occurs when the amplitude of the contractions exceeds 2 standard deviations from normal. The contractions proceed in an organized manner, propelling food down the esophagus. These patients often present with chest pain, but they present with dysphagia less often than patients with DES. 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 DES and nutcracker esophagus may overlap and can be distinguished only by motility study.

Frequency
United States

The true incidence of esophageal spasm cannot be determined. 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

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

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 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.

Race

This condition seemingly is more common in whites.

Sex

This condition may be more common in women than in men.

Age

This condition is rare in children, and incidence increases with age.

Clinical
History

Esophageal spasm usually presents with the following intermittent symptoms:

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Noncardiac chest pain (Less than 10% of causes of noncardiac chest pain are due to DES.) 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 About 20% of patients will report heartburn. A correlation between uncoordinated contractions and chest pain is difficult to document.

Physical

Physical examination is not helpful for making a diagnosis.

Causes

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. Microvascular compression of the Vagus nerve in the brainstem has been demonstrated in current research as the possible triggering event. Medical therapy may focus on these blood vessels instead of on the muscles in the esophagus.

Differential Diagnoses
Achalasia Angina Pectoris Esophageal Cancer Esophageal Diverticula Esophageal Motility Disorders Esophageal Stricture Esophageal Webs and Rings Esophagitis Gastroesophageal Reflux Disease Myocardial Infarction

Other Problems to Be Considered

Studies using catheter-based high-frequency ultrasound imaging have shown an increase in the baseline muscle thickness in patients with DES, nutcracker esophagus, and achalasia, as well as in patients with esophageal symptoms and normal static manometry. Esophageal spasm can modify cardiac function and vice versa. Esophageal spasm and coronary artery disease may coexist. Mechanisms that cause esophageal spasm can feed back to cause coronary spasm, and coronary spasm may feed forward to cause further esophageal spasm.

Workup
Laboratory Studies

Laboratory evaluation usually does not aid in the diagnosis if patients' history and physical examination 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 sugar and hemoglobin A1C 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.

Imaging Studies

Barium swallow

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Barium swallow is the best imaging study to aid in the diagnosis of esophageal spasm. Upon barium swallow, DES has a characteristic appearance of multiple simultaneous contractions. This is often referred to as a corkscrew appearance (see Media file 1).

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Unlike in DES, the barium swallow findings for nutcracker esophagus are not specific.

CT scan

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Nino-Murcia and colleagues demonstrated thickening of the esophagus with CT scan studies in patients with esophageal spasm.22 Muscular hypertrophy has been documented in some patients with DES 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.

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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.

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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.

Ultrasound

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Catheter-based high-frequency intraluminal ultrasound imaging assesses both the sensory function and the motor function of the esophagus. This imaging modality may be useful to distinguish between DES, nutcracker esophagus, and achalasia.

Other Tests

Manometry

Manometry is the best modality to help diagnose DES. 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.

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Contraction amplitude is normal. Media file 2 is a normal manometric tracing, and Media file 3 is an example of DES. 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 Media file 4).

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There may be a disassociation between symptoms and manometric findings. Esophageal electrical impedance recordings show abnormal transit in DES. Esophageal manometry may be combined with multichannel intraluminal impedance to obtain pressure and bolus transit information. About one half of patients with DES have normal transit for liquids and fluids, one fourth have abnormal transit for one substance, and one fourth have abnormal transit for both.

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

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

Treatment
Medical Care
Medical and surgical options are available for the treatment of DES and nutcracker esophagus and have been used with moderate success. Each treatment has a high failure rate, which drives the constant search for a better treatment. Medical treatment consists of calcium channel blockers, tricyclic antidepressants, nitrates, botulinum toxin, and dilatation. These conditions are usually not progressive but may interfere with the patient's quality of life.

Calcium channel blockers can reduce the amplitude of the contractions.

In patients with nutcracker esophagus, calcium channel blockers effectively reduce the amplitude of the contractions, but the chest pain may not always be reduced. Traditionally, calcium channel blockers were thought to decrease the contractions.

Nitrates also have been used with some success.

The mechanism of action is unknown but may be related to decreasing vasospasm in the brainstem, similar to calcium channel blockers.

Some patients benefit from sublingual nitroglycerin for acute symptoms of esophageal spasm.

Tricyclic antidepressants, specifically imipramine, have been shown to decrease chest

pain with no apparent cause on angiogram. Studies specifically evaluating nutcracker esophagus are not yet available.

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. The effect is temporary, and the response decreases with repeated injections.

Balloon dilatation is commonly used for achalasia, but it has been used to treat DES and
nutcracker esophagus.

Proton pump inhibitors effectively reduce or alleviate the symptoms of gastroesophageal

reflux disease, which may mimic DES. A trial of acid lowering therapy may be undertaken prior to instigating other treatments. Although treatment is often ineffective, the symptoms from DES and nutcracker esophagus usually improve over time.

The studies are small, the relief is not uniform, and symptoms recur. Dilation with mercury-filled bougies has been used in the past.

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 DES.

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Myotomy should be used with caution in patients with nutcracker esophagus because it may worsen the symptoms. 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 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 floppy Nissen.

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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.

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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 should be performed only after other treatments have been exhausted.

Diet

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

Medication
Medical therapy is the first line of treatment for esophageal spasm. Because the etiology is unknown, all medical therapies are directed at symptoms, not etiology. Proton pump inhibitors may be useful if there is 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.

Calcium channel blockers

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

Diltiazem (Cardizem)

FDA-approved for hypertension, vasospastic angina, and chronic stable angina. Decreases calcium ion flux across cell membranes in smooth muscle, thereby relaxing vascular smooth muscle.

Adult

Dosing Interactions Contraindications Precautions

Initial: 120 mg PO qd; titrate to effect without significant adverse effects; optimal dose not known
Pediatric

Not recommended

Dosing Interactions Contraindications Precautions Dosing

Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

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

Isosorbide dinitrate (Dilatate SR, Isordil)

Approved indication is for angina pectoris. Relaxes vascular smooth muscle by stimulating intracellular cyclic GMP. By decreasing left ventricular pressure and dilating arteries, reduces cardiac oxygen demand.

Adult

Dosing Interactions Contraindications Precautions

5 mg PO ac or 2.5 mg SL pc
Pediatric

Not established

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

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

Imipramine (Tofranil)

Decreases pain in patients with chest pain with no apparent cause on angiogram, which may be esophageal spasm. This is not an FDA-approved use. Mechanism of action is not known. Primary use of imipramine is in the treatment of depression.

Adult

Dosing Interactions Contraindications Precautions

25 mg PO qhs; titrate to effect as tolerated

Pediatric

Not recommended

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions

Toxins (botulinum toxin)

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

Botulinum toxin (BOTOX)

Treats excessive abnormal contractions associated with blepharospasm. Binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which, in turn, inhibits transmission of impulses in neuromuscular tissue.

Adult

Dosing Interactions Contraindications Precautions

Initial dose: 20 U have been used; reexamine patients at 7-14 d to assess for response; increase dose 2-fold over previous dose for patients experiencing incomplete paralysis of target muscle; not to exceed 25 U when administering as single injection or 200 U as cumulative dose in 30-d period; approved for strabismus and blepharospasm
Pediatric

<12 years: Not established >12 years: Administer as in adults

Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions