Practical Approaches to Dysphagia Caused by Esophageal Motor Disorders Amindra S. Arora, MB BChir and Jeffrey L. Conklin, MD Address nonspecific esophageal motor disorders (NSMD), diffuse Division of Gastroenterology and Hepatology, Mayo Clinic, esophageal spasm (DES), nutcracker esophagus (NE), 200 First Street SW, Rochester, MN 55905, USA. hypertensive lower esophageal sphincter (hypertensive E-mail: [email protected] LES), and achalasia [1••,3,4••,5•,6]. Out of all of these Current Gastroenterology Reports 2001, 3:191–199 conditions, only achalasia can be recognized by endoscopy Current Science Inc. ISSN 1522-8037 Copyright © 2001 by Current Science Inc. or radiology. In addition, only achalasia has been shown to have an underlying distinct pathologic basis. Recent data suggest that disorders of esophageal motor Dysphagia is a common symptom with which patients function (including LES incompetence) affect nearly present. This review focuses primarily on the esophageal 20% of people aged 60 years or over [7••]. However, the motor disorders that result in dysphagia. Following a brief most clearly defined motility disorder to date is achalasia. description of the normal swallowing mechanisms and the Several studies reinforce the fact that achalasia is a rare messengers involved, more specific motor abnormalities condition [8•,9]. However, no population-based studies are discussed. The importance of achalasia, as the only exist concerning the prevalence of most esophageal motor pathophysiologically defined esophageal motor disorder, disorders, and most estimates are derived from people with is discussed in some detail, including recent developments symptoms of chest pain and dysphagia. A recent review of in pathogenesis and treatment options. Other esophageal the epidemiologic studies of achalasia suggests that the spastic disorders are described, with relevant manometric worldwide incidence of this condition is between 0.03 and tracings included. In recent years, the importance of 1.1/105/year [9]. The prevalence of diffuse esophageal gastroesophageal reflux as a primary cause of esophageal spasm is similar to that of achalasia, whereas other dysmotility has been recognized, and this is also discussed. disorders (eg, nutcracker esophagus and nonspecific eso- In addition, the motility disturbances that develop after phageal motility disorders) are more common [1••,4••]. surgical fundoplication are reviewed. This review focuses on the normal mechanism whereby the esophagus contracts. The various motility disorders are then discussed, followed by disorders of swallowing caused Introduction by gastroesophageal reflux disease (GERD) and the The esophagus and its sphincters serve to transport food surgical treatments used for GERD. boluses from the pharynx to the stomach and to protect the upper aerodisgestive tract from the reflux on noxious gastric contents. The act of swallowing is comprised of an Esophageal Motility elaborately timed series of events requiring intact central, Central neural stimulation studies clearly demonstrate that autonomic, and enteric nervous systems as well as a set of the motor nuclei providing innervation to the muscles functional striated and smooth muscles [1••,2,3,4••]. Any used in swallowing are located in the brainstem. However, interference with these precise mechanisms will result in the neural circuitry is complex, as direct stimulation of dysphagia (dys = abnormal, phagia = swallow). This article these motor nuclei does not produce swallowing directly concentrates on the esophageal motor disorders that result [7••,10,11•]. The following section describes the anatomy in dysphagia. In addition, the various forms of therapy and electrical physiology of the esophagus. available to treat these problems are discussed. Disorders of esophageal motility have been described Anatomy and physiology of the esophagus for centuries. Furthermore, disordered esophageal motility The elastic pharyngeal layer becomes the muscularis has been linked to various “chest spasms” as well as dys- mucosa of the esophagus at the level of the cricoid carti- phagia. Only recently, in the latter half of the twentieth lage. In humans, the muscularis mucosa is a thin muscular century, has the technology to monitor the esophageal layer that is positioned just beneath the mucosa. Although motor response been applied regularly to patients. Using it is the innermost component of the neuromuscular appa- esophageal manometric equipment, a number of motor ratus of the esophagus, it plays little role in the esophageal disorders have been described. These conditions include, motor function [12]. The submucosa is located deep in the 192 Esophagus muscularis mucosa, and is covered by the inner circular Esophageal peristalsis is a stereotyped event. It starts and outer longitudinal fibers of the muscularis externa. with the longitudinal muscles of the esophagus contracting Striated muscle comprises the proximal 5% of the muscu- in sequence to produce a shortening of the esophagus. A laris externa; the next 40% is a mixture of smooth and ring-like contraction of the circular muscles then sweeps striated muscles in varying proportions, and the distal 55% along the esophagus to propel the bolus to the stomach. to 60% is comprised solely of smooth muscle [12]. The The primary peristaltic wave is thought to arise from an myenteric plexus of Auberbach is a flat neural network of initial hyperpolarization of the circular smooth muscle ganglia and interconnecting nerve fibers located between down the length of the smooth muscle. This wave of hyper- the longitudinal and circular layers of the esophagus. The polarization is triggered by swallowing, starts nearly simul- nerve cells of the myenteric plexus receive inputs from taneously at all levels of the smooth muscle esophagus, and other neurons within the plexus and from the central ner- results from the release of nitric oxide (NO) from myenteric vous system (CNS). Myenteric neurons send axons to the neurons innervating the circular smooth muscle cells. It smooth muscle of the esophagus and other neurons within is quickly followed by a depolarization that generates a the plexus. The density of nerve fibers innervating the rebound contraction of the smooth muscle. The peristaltic smooth muscle esophagus is highest at the proximal edge contraction wave is generated because the duration of the of the smooth muscle segment and decreases substantially hyperpolarization increases along the length of the before reaching the gastroesophageal junction. In addi- esophagus. Secondary peristalsis is formed by esophageal tion, some ganglia are found in the striated portion of the contractions that arise in the absence of a swallow and is an esophagus, the function of which is still unknown. There is entirely intramural event during which the vagus nerve is no submucosal plexus of Meissner in the esophagus, inactive [16]. Tertiary peristalsis (or autonomous perist- unlike the rest of the gastrointestinal (GI) tract [12,13••]. alsis) occurs in the extrinsically denervated esophagus. The striated muscles of the pharynx and esophagus Before leaving our discussion of the neuromuscular receive their extrinsic innervation from vagal neurons, the function of the various regions of the esophagus, it is cell bodies of which are located in the nucleus ambiguus of important to mention that the motor output from both the the brainstem. These axons innervate the striated muscle vagus nerve and the sympathetic nervous system can fibers in the form of motor endplates [10,11•]. On the other be modulated by the sensory innervation arising within hand, the extrinsic nerve supply to the smooth muscle of the the esophagus. In the cervical esophagus, sensory afferents esophagus is derived from the dorsal motor nucleus of the travel to the CNS with the superior laryngeal nerve, whereas vagus. These parasympathetic preganglionic fibers travel the more distal esophageal sensory information is carried down the vagus and form a synapse on neurons within the by the recurrent laryngeal nerve or esophageal branches of plexus of Auberbach. Modulation of the neural activity of the the vagus. Recent studies demonstrate that a number of plexus of Auerbach is further enhanced by sympathetic fibers esophageal motor disorders are associated with a variety of originating from the superior cervical ganglion (from T4 to neural defects involved in the central processing of infor- T6) and traveling with the vagal fibers [10,11•,12]. mation. For instance, patients with diffuse esophageal The coordinated activity of the neuromuscular apparatus spasm and nutcracker esophagus have abnormal cortical produces a peristaltic wave within the esophagus. The evoked potentials in response to esophageal stimulation as primary peristaltic wave is triggered in the CNS, as bilateral well as abnormal esophageal motor evoked potentials in vagotomies will abolish it. The progression of the peristaltic response to cerebral stimulation [17•]. wave down the esophagus follows an innate pathway. The The lower esophageal sphincter is defined manometric- striated muscles within the upper esophagus only receive an ally as a zone of high pressure between the esophagus and excitatory input from the medullary swallowing center via stomach that relaxes with swallowing. The circular muscles the vagus nerve [10,11•,12,13••,14,15]. The patterned acti- of the LES, unlike the rest of the esophagus, are tonically vation of these neurons in the swallowing center results in