Esophageal motility is a complex and multifactorial process that functions to pass food and liquid through the esophagus. Using systematic contractions in the esophageal body, combined with an appropriately timed relaxation of the lower esophageal sphincter (LES), the bolus is able to pass from the esophagus into the stomach. Errors in the process can occur anywhere along this chain of events and can lead to significant morbidity for patients. The constellation of presenting symptoms includes dysphagia, chest pain, and reflux. Due to these often vague symptoms, many patients undergo multiple other therapies prior to being diagnosed with an esophageal motility disorder and ultimately go on to further treatment. It is reasonable to start with a short course of acid suppression therapy in patients; however, when their symptoms fail to improve, this should prompt additional workup.

Achalasia is by far the most commonly diagnosed disease of esophageal motility; however, numerous other dysmotility patterns exist. The advent of high-resolution manometry has led to new understanding of esophageal function. In addition, the information obtained from advanced diagnostics has led to improved patient selection for the various management options available. This chapter will review the common esophageal motility disorders, their diagnosis, and their management.

A normal esophagus varies from 18 to 25 cm in length and serves to transport food from the oropharynx to the stomach. Structurally, the esophagus is made up of 4 primary layers, including the innermost mucosa, submucosa, muscularis propria, and adventitia. The muscle layer includes the innermost circular fibers and the outer longitudinal fibers, of which the upper third consists mostly of striated muscle, whereas the lower two-thirds are primarily smooth muscle. In addition to the circular and longitudinal muscles, the esophagus also contains 2 muscular sphincters. The upper esophageal sphincter controls the entrance of food to the esophagus from the oropharynx, whereas the LES prevents reflux of acid contents into the esophagus from the stomach.

Normal esophageal function is a complicated and well-choreographed event. When food is swallowed, the epiglottis moves backward to prevent aspiration and to direct food into the esophagus all while the upper esophageal sphincter relaxes. Primary peristalsis transfers the bolus down the esophagus by rhythmic contractions, which are controlled by excitatory activity in the vagal nucleus ambiguous, which releases acetylcholine.¹ In coordination and prior to the excitatory signal, inhibitory neurons (which release nitric oxide and vasoactive intestinal peptide) are activated by the preganglionic neurons and provide deglutitive inhibition. As one moves further down the esophagus toward the stomach, there is an increased inhibitory action called the latency gradient.² This delays contractions and allows the bolus to move forward toward the stomach. In contrast to primary peristalsis, secondary peristalsis is elicited by esophageal distension and is a local reflex that independently causes contraction of the esophagus. It is the relationship of inhibitory and excitatory signals along the esophagus that provides the coordinated forward movement of the food bolus. A disruption of this balance is thought to lead to esophageal motility disorders such as achalasia.³

Esophageal motility disorders make up a broad spectrum of diseases with varied presentations and symptoms. Initial differentiation divides them into primary motility disorders versus secondary motility disorders that are manifestations of systemic diseases. By far, the most well-described primary motility disorder is achalasia, which results from failure of the LES to relax and causes varied esophageal contractions. Other primary motility disorders to be discussed in this chapter include diffuse esophageal spasm and nutcracker esophagus.

Epidemiology

Achalasia is the most well-studied esophageal motility disorder, with an estimated incidence of 1 per 100,000 worldwide.^4-6 However, achalasia is a chronic disease, and as a result, the prevalence is estimated to be between 9 and 10 per 100,000 people.^5,7 Sex and race do not appear to have a significant impact on the incidence of achalasia. However, there is increasing evidence supporting a genetic role.^8,9 This finding comes from twin and sibling studies and from association of achalasia with other diseases such as Parkinson disease and Down syndrome. However, genetic testing in achalasia is limited primarily to research studies with limited diagnostic utility.

Pathophysiology

The cause of achalasia is felt to be the functional loss of myenteric plexus ganglion cells of the distal esophageal sphincter and lower esophagus.¹⁰ This leads to a loss of inhibitory signals and eventually unopposed excitatory signals and the inability of the LES to relax. Although a definitive cause is unknown, most researchers feel that it is an autoimmune process that leads to loss of the myenteric plexus.¹¹ This is supported by histologic exam in which the ganglion cells that do remain are often surrounded by lymphocytes and eosinophils.^12,13 In addition, some patients with achalasia also experience dysfunction of the upper esophageal sphincter, leading to difficulty with belching.¹⁴ In unaffected patients, when gas from the stomach enters the esophagus, it triggers a relaxation of the upper esophageal sphincter. However, in some patients with achalasia, this reflex is lost presumably due to the loss of inhibitory neurons. This may also be a contributing factor to esophageal distension seen in patients with chronic achalasia. Finally, although rarely seen in Western countries, Chagas disease is a well-known cause of achalasia.¹⁵ Secondary to an infection with the parasite Trypanosoma cruzi, Chagas disease leads to widespread myenteric plexus destruction and subsequently achalasia.

Signs and Symptoms

For most patients, achalasia has an insidious onset with gradual progression of symptoms. Most commonly, this includes dysphagia that progresses from solids to liquids, and patients can often go years before seeking appropriate medical attention.¹⁶ Patients frequently undergo therapy for other diseases such as gastroesophageal reflux disease before being diagnosed with achalasia.¹⁷

The most common symptoms associated with achalasia include dysphagia to solids (91%) and liquids (85%) and regurgitation of food and saliva (45%-75%; Table 22-1).^18,19 Although dysphagia is seen in nearly all patients with achalasia, it can also be observed in up to 4% of adults in the United States.²⁰ After dysphagia, additional nonspecific symptoms include chest pain, epigastric pain, weight loss, and odynophagia. Although not clearly diagnostic of achalasia, these symptoms are often part of the clinical picture.

Respiratory symptoms are also occasionally seen in patients with achalasia and are thought to be related to chronic aspiration due to failed clearance of food and liquid from the esophagus. Symptoms including sore throat, hoarseness, or postnasal drip are seen in up to 71% of patients, and cough is seen in 61% of patients.²¹ However, most patients who report respiratory symptoms often have had symptoms of dysphagia for 2 or more years prior to the onset of their respiratory symptoms.²¹

Finally, patient demographics may alter patient symptoms at presentation. Younger patients often present with symptoms of chest pain and heartburn more frequently than older patients.²² In addition, older patients tend to be overall less symptomatic than their younger counterparts. Finally, obese patients with a body mass index ≥30 kg/m² often experience symptoms of choking and vomiting more frequently before myotomy compared with nonobese patients.²³

Diagnosis and Workup

Patients who initially present with complaints of dysphagia are often initially trialed on a course of a proton pump inhibitor (PPI). Although this is appropriate, when symptoms fail to improve after a 4 to 6 weeks, further evaluation is warranted. For most patients, the appropriate next step would be to proceed with an upper endoscopy with mucosal biopsy. This is crucial to rule out any underlying inflammatory ring, erosive gastroesophageal reflux, eosinophilic esophagitis, and esophageal cancer. The entity of an esophageal structural abnormality leading to achalasia symptoms is termed pseudoachalasia. Other endoscopic findings often seen in patients with achalasia include a dilated and tortuous esophagus, residual food and fluid in the esophagus, and difficulty passing food and fluid through the LES (Fig. 22-1). Finally, patients with achalasia often develop Candida esophagitis secondary to the stasis.

Although endoscopic findings can be suggestive of achalasia, additional evaluation with barium esophagram is recommended. This can provide details on both anatomy and function of the esophagus. A classic “bird beak” presentation (Fig. 22-2) can often be seen in patients with achalasia; other findings on esophagram include a dilated esophagus with aperistalsis and a corkscrew appearance in more severe cases. Similar to endoscopy, although these findings are suggestive of achalasia, they are insufficient for a definitive diagnosis. The next step in evaluation should include esophageal manometry.

Traditional manometry, which includes water-perfused and strain gauge systems, has been for the most part replaced with more modern, reproducible,²⁴ and accurate²⁵ high-resolution manometry (HRM) catheters. Specifically, HRM catheters have sensors spaced every 1 cm along the length of the catheter, in contrast to every 3 to 5 cm seen in traditional manometry. The result of the study is an esophageal pressure topography, which reports the pressure in a color scale compared with time and location within the esophagus (Fig. 22-3). These catheters are placed either directly or under endoscopic guidance (Fig. 22-4) through the LES and into the stomach to facilitate measuring the pressure of the distal esophagus and LES. Manometric findings consistent with achalasia include incomplete relaxation of the LES, which distinguishes it from other disorders associated with aperistalsis. In normal individuals, there is complete relaxation of the LES during a swallow (to a measured level <8 mm Hg above gastric pressure). However, in patients with achalasia, the LES relaxation during swallow may be incomplete or absent all together. Additional manometric findings consistent with achalasia include an elevated resting LES pressure of >45 mm Hg and aperistalsis in the distal two-thirds of the esophagus.²⁶

More widespread use and investigation of HRM have led to the ability to subtype achalasia based on the patterns of esophageal pressurization and the creation of a new classification scheme for motility disorders called the Chicago Classification.²⁷ The ability to subtype patients with achalasia has enabled the development of clinically relevant phenotypes.²⁸

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  Type I (classic) achalasia: Impaired LES relaxation, absent peristalsis, and normal esophageal pressure

  
  
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  Type II achalasia: Impaired LES relaxation, absent peristalsis, and increased panesophageal pressure

  
  
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  Type III (spastic) achalasia: Impaired LES relaxation, absent peristalsis, and distal esophageal spastic contractions

When evaluating the different subtypes, it has been found that type II patients were significantly more likely to respond to any therapy (Botox, 71%; pneumatic dilation, 91%; or Heller myotomy, 100%) than type I (56% overall) or type III patients (29% overall).²⁸ This information has improved our ability to discuss expected outcomes with our patients.

In cases without a clear diagnosis after endoscopy, barium esophagram, and manometry, there may be benefit from additional evaluation of the LES by endoscopic ultrasound²⁹ or timed barium esophagram to document contrast bolus retention.

Treatment

There is no cure for achalasia; rather, treatment is aimed at palliating the symptoms that patients experience. Therapies are directed at reducing the contractility in the LES, thus allowing for adequate esophageal emptying. Overall, the goal is early diagnosis and therapy to prevent late complications while preserving esophageal function.

MEDICAL

Medical therapy is the least invasive but also least effective treatment option for patients with achalasia, and as such, it is reserved for patients who cannot tolerate other treatments. Although initial response to medical therapy is approximately 50%, long-term success is limited by side effects, which include headache, orthostatic hypotension, and edema. The primary medical therapy for achalasia includes oral calcium channel blockers or nitrates, which can result in relaxation of the LES pressure in up to 47% to 64% of patients.³⁰ Nifedipine (10-30 mg administered 30-45 minutes before meals) and isosorbide dinitrate (5-10 mg administered 10-15 minutes before meals) are the 2 most widely used medical therapies; however, some studies suggest that isosorbide dinitrate may provide a more rapid response.³¹

Finally, phosphodiesterase-5 inhibitors, such as sildenafil, have also been used to treat patients with achalasia. They have been found to inhibit the contractile activity of the esophageal musculature in patients with achalasia, resulting in decreased LES tone.³² Although initial studies have suggested some symptom improvement, long-term results are lacking.

BOTULINUM TOXIN

Botulinum toxin therapy is considered for patients who are not good candidates for more definitive therapy such as pneumatic dilation or surgical or endoscopic myotomy. Under endoscopic guidance, botulinum toxin is injected into the LES and ultimately blocks the excitatory (acetylcholine-releasing) neurons that lead to the increase in the LES smooth muscle. The overall effect is a decrease in the resting pressure of the LES, allowing the esophagus to empty into the stomach. Initial symptom improvement rates of botulinum toxin are similar to those of pneumatic dilation and approach 70%.³³ However, patients tend to have more frequent recurrence of symptoms in as little as 6 months.³⁴ Finally, it has been found that repeated botulinum toxin injection may make subsequent myotomy more difficult and possibly result in worse outcomes compared to patients who undergo myotomy alone.³⁵