Chapter 393. Disorders of Esophageal Motility

Esophageal motility disorders are classified as primary when they are one of a small number of isolated disorders of motility that include achalasia, diffuse esophageal spasm, nutcracker esophagus, and nonspecific esophageal motility disorders of the esophagus or as secondary when associated with known disease processes (Table 393-1). A basic understanding of normal esophageal motility allows appreciation of the diagnostic criteria for various motility disorders.

The esophagus is a dynamic muscular conduit connecting the oropharynx to the stomach. Two sphincters, the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), divide the esophagus from the oropharynx and stomach respectively. The esophagus is composed of striated muscle in the upper third and smooth muscle in the lower two thirds. Similar to the remainder of the gastrointestinal tract, the smooth muscle portions of the esophagus are divided into 2 layers: the innermost arranged in a circular pattern and the outer aligned along the longitudinal axis. Each layer is thought to perform a unique function. The circular muscle layer collapses the lumen of the esophagus and is responsible for generating contractile pressure, while the longitudinal layer shortens the esophagus and may play a role in opening the LES. The UES consists of C-shaped bundles of muscle fibers from the cricopharyngeus muscle. The LES consists of components from the esophagus, stomach, and skeletal muscle from the diaphragm. At rest, the pressure within the esophagus reflects the intrathoracic pressure and is therefore slightly negative during inspiration and slightly positive during expiration. Closure of the UES prevents swallowing of air, and closure of the LES prevents reflux of gastric contents during inspiration. The pressure that is tonically maintained by the UES varies tremendously, being almost absent during sleep and increasing to over 100 mm Hg with emotional stress, straining, or when the esophagus is distended or perfused with acid fluid. The LES maintains a pressure of approximately 20 mm Hg, with values below approximately 10 mm Hg being abnormal. LES pressure is augmented during inspiration by contraction of the diaphragm. The LES tone is decreased by anesthesia, morphine, diazepam, β-adrenergic agents, dopamine, secretin, cholecystokinin, glucagon, vasoactive inhibitory peptide, progesterone and estrogen, nitrites, nifedipine, theophylline, intraduodenal fat, ethanol, and nicotine. Relaxation of the LES appears to be mediated by the actions of vasoactive inhibitory peptide and/or nitric oxide.

Coordination of the muscles of the pharynx, UES, esophagus, and LES are required for propulsion of food and liquid bolus to the stomach. Swallowing induces relaxation and opening of the UES to allow transfer of food and liquid bolus from the pharynx into the upper esophagus. This is followed by a vagally mediated sequential contraction of the muscles in the esophageal body—termed primary peristalsis—and forms a pressure wave with amplitudes of 50 to 110 mm Hg that travels down the esophagus at a rate of approximately 3 cm/s. Peristalsis progresses through the entire length of the esophagus unless aborted because of a second swallow that occurred during the primary peristalsis wave. Similar to the UES, the LES relaxes with initiation of the swallow to allow the bolus to enter the stomach. Distension of the esophageal body wall stimulates secondary peristalsis, which is identical to primary peristalsis except that there is no swallow, pharyngeal contraction, or UES relaxation/contraction.

Relaxation of the LES that is not associated with swallowing is termed transient lower esophageal sphincter relaxation (TLESR). These episodes are stimulated by gastric distension, so the frequency of TLESRs normally increases postprandially. LES relaxations are accompanied by crural diaphragm relaxation, thus abolishing the tone at the gastroesophageal junction. TLESRs are an important protective mechanism, allowing belching or burping. However, TLESRs are also the main mechanism for gastroesophageal reflux in infants, children, and adults.1,2 The TLESRs are suppressed when a person is supine.

Primary esophageal motility disorders are uncommon in otherwise healthy children. Dysphagia, chest pain, or recurrent foreign-body obstruction are the usual modes of presentation, although failed esophageal peristalsis can result in spilling of residual food into the airway with symptoms of recurrent aspiration pneumonia. Diagnosis is often suspected following an esophagram, which is a dynamic study that shows the absence of an anatomic obstruction and may show abnormal peristalsis. Esophageal manometry is required for a specific and conclusive diagnosis (Fig. 393-1).

Achalasia

Achalasia is a motor disorder of the esophagus with characteristic radiographic features on barium swallow (a dilated esophagus with air fluid levels and a stereotypical “birds-beak” appearance at the gastroesophageal junction) (eFig. 393.1) and manometric findings as shown in Figure 393-1. The manometric findings of achalasia include incomplete relaxation of the lower esophageal sphincter and lack of normal esophageal peristalsis. More recently, increased muscle mass has been noted with ultrasonographic evaluation of the esophagus. The pathophysiology of achalasia is not certain, but it seems likely that in many cases it is due to an autoimmune-mediated process resulting in a loss of inhibitory relaxation of the LES. Congenital or syndromatic cases likely have a separate etiology with specific genetic abnormalities being identified in some associated syndromes (see below). Presenting symptoms include dysphagia, regurgitation, recurrent pneumonia, weight loss, and chest pain. The pathophysiology of achalasia is not certain, but it seems likely that in many cases it is due to an autoimmune-mediated process resulting in a loss of inhibitory relaxation of the LES. Congenital or syndromatic cases likely have a separate etiology with specific genetic abnormalities being identified in some associated syndromes (see below). Histologic specimens reveal a decrease in nitric oxide synthetase neurons containing calcitonin gene–related peptide, vasoactive intestinal peptide, and nitric oxide in the myenteric plexus of the distal esophagus.3 Autoantibodies against neurons, CD3/CD8 predominant lymphocytic infiltrates, and evidence of complement cascade activation has been found in the myenteric plexus in patients with achalasia.4,5 Neuronal loss of neurons containing calcitonin gene–related peptide, vasoactive intestinal peptide, and nitric oxide is most marked. The overall incidence of achalasia is 0.4 to 0.6 per 100,000, with only about 5% of cases occurring in children and the average age of diagnosis being about 9 years old. Achalasia occurs in association with other disorders and syndromes, as listed in Table 393-2. Chagas disease can be indistinguishable from achalasia and should be considered in patients who have traveled to endemic areas, including the southern United States and Latin America. Early presentation of achalasia is frequently associated with an autosomal recessive syndrome of deafness, vitiligo, short stature, and muscle weakness, or with the syndrome of alacrima and corticotropin insensitivity (Allgrove syndrome, or triple-A syndrome, which has been linked with mutations on 12q13). Achalasia is also reported as part of Alport syndrome and in children with Down syndrome.6 Rare cases of familial achalasia and of familial coexistence of achalasia and other esophageal motility disorders have been reported.7 Achalasia has also been associated with autoimmune polyendocrinopathy syndrome and multiple endocrine neoplasia type 2B. Leiomyoma or other tumors of the stomach may masquerade as achalasia. Achalasia has also been associated with familial visceral neuropathies, familial dysautonomia, Sjogren syndrome, adrenoleukodystrophy and Addison disease.

Surgical treatment with a Heller myotomy (usually with an antireflux procedure) is becoming the treatment of choice for achalasia.8 Pneumatic balloon dilation of the LES9 ruptures the muscle and may provide long-term relief from symptoms; however, repetitive treatments often are necessary. Similarly, injection of the LES with botulinum toxin10 provides transient relief, but the requirement for repeated treatment makes these therapies less attractive for treatment of childhood achalasia. Pharmacotherapy (eg, nifedipine) is variably effective and rarely provides an option for long-term management. Following treatment for achalasia, some degree of dysphagia for solids often persists because of persistent aperistalsis of the esophagus. This requires that patients chew food well and often need liquid chasers to clear the esophagus. There is also a long-term risk of esophagitis, Barrett esophagus, and esophageal adenocarcinoma requiring consistent, long-term follow-up through adulthood.

Other Primary Esophageal Motility Disorders

Diffuse esophageal spasm (prolonged simultaneous contractions of the esophagus) and high-amplitude esophageal contractions (> 180 mm Hg, also called nutcracker esophagus) are rarely described in children. Treatment with anticholinergics, nitroglycerin, long-acting nitrates, nifedipine and botulinum toxin injection, and surgery all have inconsistent reported efficacy with minimal pediatric experience. Nonspecific esophageal motility disorders are characterized by varying combinations of abnormalities, but the clinical and pathologic relevance of these disorders are not clear.

Gastroesophageal reflux disease11 and other inflammatory disorders of the esophagus produce various motor abnormalities (such as conduction defects, abnormal esophageal contraction waveforms, low-pressure waves, incomplete peristalsis, and either low or high LES pressure). Esophageal motor disorders are also common in other systemic diseases (see Table 393-2) and in children with intestinal pseudoobstruction and esophageal atresia.12,13 Diagnosis and aggressive treatment of the underlying disorder may normalize motility.