Continuing Education Activity

Major disorders of motility are usually universally symptomatic and have a deleterious impact on the patient's quality of life. Prompt action is needed to diagnose the illness promptly to stop its progression and to initiate appropriate treatment. This activity examines the presentation, diagnosis, management, and challenges clinicians can face with these patients.

Objectives:

• Identify some potential etiologies of esophageal motility disorders.
• Review the steps to follow for the evaluation of esophageal motility disorders.
• Outline some management options available for esophageal motility disorders.
• Summarize interprofessional team strategies for improving care coordination and communication to improve outcomes in managing esophageal motility disorders.

Introduction

The esophagus is a tube-like structure that transports food and other edibles from the mouth to the stomach. This is accomplished through the sequential and well-coordinated movement of food from the proximal esophagus to the distal esophagus and finally into the stomach. Disruption in this well-coordinated movement results in a variety of esophageal motility disorders, which are further classified as either primary or secondary[1].

It is approximately 25 cm long anatomically and has two sphincters, one at the proximal upper part and the other at the distal end.[2] The upper esophageal sphincter (UES) is a striated muscle that prevents air from entering the stomach. The lower esophageal sphincter (LES) is made up of smooth muscles with baseline tonicity that prevents gastric content from refluxing into the esophagus. The esophageal body is made up of two types of muscles: striated muscles in the proximal portion and smooth muscles in the distal portion. The transition from skeletal to smooth muscles occurs in the mid-esophagus. These muscles are divided into two parallel layers: outer longitudinal and inner circular.  Peristalsis is the coordinated contraction of these two layers that propels the intraluminal esophageal content into the stomach.

Etiology

Esophageal motility disorders can be broadly subdivided into two categories:

1. Primary disorders (due to esophageal diseases per se)
2. Secondary phenomena (esophageal dysfunction is part of more global disease, such as in pseudo-achalasia(tumor, compression, etc.), Chagas disease, and PSS (scleroderma).

The motility disorders can also be classified based on the site of pathology:-

I. Oropharyngeal dysphagia (oropharynx is the site)

Neuromuscular[3]

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig disease)
• CNS tumors (benign or malignant)
• Idiopathic UES dysfunction
• Manometric dysfunction of the UES or pharynx†
• Multiple sclerosis
• Muscular dystrophy
• Myasthenia gravis
• Parkinson disease
• Polymyositis or dermatomyositis
• Postpolio syndrome
• Stroke
• Thyroid dysfunction

Structural

• Carcinoma
• Infections of pharynx or neck
• Osteophytes and other spinal disorders
• Prior surgery or radiation therapy
• Proximal esophageal web
• Thyromegaly
• Zenker diverticulum

Neuromuscular (Motility) Disorders

Primary

• Achalasia
• Distal esophageal spasm
• Hypercontractile (jackhammer) esophagus
• Hypertensive LES
• Nutcracker (high-pressure) esophagus

Secondary

• Chagas disease
• Reflux-related dysmotility
• Scleroderma and other rheumatologic disorders

STRUCTURAL (MECHANICAL) DISORDERS

Intrinsic

• Carcinoma and benign tumors
• Diverticula
• Eosinophilic esophagitis
• Esophageal rings and webs (other than Schatzki ring)
• Foreign body
• Lower esophageal (Schatzki) ring
• Medication-induced stricture
• Peptic stricture

Extrinsic

• Mediastinal mass
• Spinal osteophytes
• Vascular compression

II. Esophageal dysphagia (mid and lower esophagus is the site)

Dysphagia due to pharyngeal or UES dysfunction can also be included in a discussion of esophageal motor disorders, but this is usually a manifestation of a more global neuromuscular disease process. The major focus of this article will be on primary motility disorders, particularly achalasia. However, mention will be made of the secondary motility disorders and proximal pharyngoesophageal dysfunction when important unique features exist.

Epidemiology

Estimates of the prevalence of dysphagia among individuals older than 50 years range from 16% to 22%, with most of this related to oropharyngeal dysfunction.

Most oropharyngeal dysphagia is related to neuromuscular disease; the prevalence of the most common anatomic etiology, Zenker diverticulum, is estimated to range from a meager 0.01% to 0.11% of the population in the USA, with a peak incidence in men between the 7th and 9th decades.[4] The consequences of oropharyngeal dysphagia are severe and include dehydration, malnutrition, aspiration, choking, pneumonia, and death. Within health care institutions, it is estimated that up to 13% of hospitalized patients and 60% of nursing home residents have feeding problems. Again, most are attributed to oropharyngeal dysfunction as opposed to esophageal dysfunction.

Mortality of nursing residents with dysphagia and aspiration can be as high as 45% over 1 year. As the U.S. population continues to age, oropharyngeal dysphagia will become an increasing problem associated with complex medical and ethical issues.

Achalasia is the most easily recognized and best-defined motor disorder of the esophagus. Modern estimates of the incidence of achalasia are about 2.9 per 100,000 population in the USA, affecting both genders equally and usually presenting between 25 and 60 years of age.[5][6] As achalasia is a chronic condition, its prevalence greatly exceeds its incidence; a recent estimate of achalasia prevalence in Chicago concluded that it might be as high as 76 per 100,000 population, given that the average age of diagnosis was 56 with an expected average survival of 26 years after diagnosis. Reports of familial clustering of achalasia raise the possibility of genetic predisposition. However, arguing against a strong genetic determinant, a survey of 1012 first-degree relatives of 159 achalasia patients identified no affected relatives. There is a rare genetic achalasia syndrome associated with adrenal insufficiency and alacrima. This syndrome is inherited as an autosomal recessive disease and manifests with the childhood-onset of autonomic nervous system dysfunction, including achalasia, alacrima, sinoatrial dysfunction, and abnormal pupillary responses light, and delayed gastric emptying.[7] It is caused by mutations in AAAS, which encodes a protein known as ALADIN.

There are no population-based studies on the incidence or prevalence of esophageal motility disorders other than achalasia.  Thus, the only way to estimate the incidence or prevalence of spastic disorders is to examine data on populations at risk and reference the observed frequency of spastic disorders to the incidence of achalasia, which, as detailed earlier, is about 2.75 per 100,000 population. In doing so, the prevalence of DES is much lower than that if modern restrictive diagnostic criteria are used.

Populations at risk for motility disorders are patients with chest pain and/or dysphagia, so it is among these patients that extensive manometric data have been collected. Manometric abnormalities are prevalent among these groups, but the manometric findings are of unclear significance in most cases.

Pathophysiology

Like the etiology, the pathophysiology of esophageal motility disorder is very hazy, except for achalasia. This applies to all primary esophageal disorders. For secondary esophageal motility disorders, esophageal pathology is better explained in the context of pre-existing underlying illness.

Achalasia

It is the only primary esophageal pathology with slightly well-known pathophysiology among all the other primary esophageal dysmotility disorders. It is characterized by impaired LES relaxation with swallowing and peristalsis in the smooth muscle esophagus. If there are premature, spastic contractions in the esophageal body, the disease is referred to as spastic (type III) achalasia. These physiologic alterations result from damage to the innervation of the smooth muscle segment of the esophagus (including the LES) with loss of ganglion cells within the myenteric (Auerbach) plexus. Several observers report fewer ganglion cells and ganglion cells surrounded by mononuclear inflammatory cells in the smooth muscle esophagus of achalasia patients. The degree of ganglion cell loss parallels disease duration, likely progressing from EGJ outflow obstruction to type II achalasia, to type I achalasia, to end-stage achalasia. Type III achalasia seems to have unique pathogenesis, characterized by myenteric plexus inflammation and altered function, but not destruction. Physiologic studies in achalasia patients suggest dysfunction consistent with postganglionic denervation of esophageal smooth muscle potentially affect excitatory ganglion neurons (cholinergic), inhibitory ganglion neurons, or both.

Regardless of excitatory ganglion neuron impairment, it is clear that inhibitory ganglion neuron dysfunction is an early manifestation of achalasia. These neurons mediate deglutitive inhibition (including LES relaxation) and the sequenced propagation of esophageal peristalsis. The ultimate cause of ganglion cell degeneration in idiopathic achalasia is gradually being unraveled, with increasing evidence pointing toward an autoimmune process in genetically susceptible individuals.59 HSV-1 has been proposed to be one of the causes of ganglion destruction

Distal Esophageal Spasm (DES)

Although the diagnosis of DES is often invoked as a cause of esophageal chest pain, the entity is actually exceedingly rare, with most cases of esophageal chest pain attributable to reflux disease or achalasia. The Chicago Classification has proposed reduced distal latency (DL) of peristalsis as the cardinal abnormality in DES. Although DES is clearly a disorder of peristalsis, the majority of afflicted patients exhibit normal peristaltic contractions most of the time. The neuromuscular pathology responsible for DES isunknown, and there are no known risk factors. The most striking reported pathologic change is diffuse muscular hypertrophy or hyperplasia in the distal esophagus with a thickening of up to 2 cm.

Hypercontractile (Jackhammer) Esophagus

Vigorous esophageal contractions with normal DL defined as esophageal hypercontractility or jackhammer esophagus in the Chicago Classification can be associated with both dysphagia and chest pain. From a clinical perspective, the summary metric for quantifying distal esophageal contractility in high-resolution manometry is the distal contractile integral (DCI). DCI values greater than 8000 mm Hg/cm/sec represent an extreme hypercontractility pattern, often associated with repetitive contractions, rarely seen in normal subjects, and almost always associated with chest pain and dysphagia. The current version of the Chicago Classification labels this condition “jackhammer esophagus” when two such contractions occur in a manometric study.

Absent Peristalsis

It is often idiopathic.

Spastic Motility Disorder

It is characterized by extensive degeneration of vagus nerve filaments, excessive deposition of collagenous material around nerve endings, and fragmentation of mitochondria. This leads to an imbalance between excitatory and inhibitory impulses in the postganglionic pathways. This is more marked in the distal two-thirds of the esophagus. It is also believed that anxiety also has a role in its pathogenesis.[8]

Scleroderma

Owing to the propensity of patients with scleroderma to have excessive deposition of fibrous tissue in various organs, the esophagus also has atrophic and fibrous changes. The muscular layer of the esophagus is gradually replaced by the fibrous scar tissue, which gradually leads to loss of peristalsis and weakening of LES. However, this phenomenon is only limited to the distal esophagus, and the motility at the proximal end is preserved.[9]

History and Physical

The patient's history is crucial in the evaluation of dysphagia. Dysphagia is a fundamental symptom of esophageal motility disorders. The absence of associated aspiration suggests esophageal (as opposed to oropharyngeal) dysphagia, cough, nasopharyngeal regurgitation, drooling, pharyngeal residue following swallow, or co-occurring neuromuscular dysfunction (e.g., weakness, paresthesia, slurred speech). On the other hand, the associated conditions of heartburn, regurgitation, chest pain, odynophagia, or intermittent esophageal obstruction suggest esophageal dysphagia. An important limitation of the patient history in esophageal dysphagia is that a patient’s identification of the location of obstruction is of limited accuracy. Specifically, a distal esophageal obstruction caused by an esophageal ring, stricture, or achalasia will often be perceived as cervical dysphagia, and patients can correctly localize distal dysfunction only 60% of the time. Because of this subjective difficulty in distinguishing proximal from distal lesions within the esophagus, an evaluation for cervical dysphagia should encompass the entire length of theesophagus.

Historical points suggestive of a motor disorder are difficulty with both solids and liquids, as opposed to only with solids, which is more suggestive of mechanical obstruction. However, the functional consequences of mechanical or inflammatory disorders can exactly mimic those of primary motility disorders. Thus, as with the evaluation of oropharyngeal dysphagia, a motility disorder should be considered as an etiology for esophageal dysphagia only after exclusion of more common diagnoses by endoscopic, histologic, and/or radiographic examination.

 The major objectives of the history are to differentiate oropharyngeal dysphagia from esophageal dysphagia, xerostomia (hyposalivation), or globus sensation. All are frequently confused with each other. Globus sensation, in particular, is frequently confused with dysphagia. Unlike dysphagia, which occurs only during swallowing, globus sensation is prominent between swallows. Patients relate the nearly constant sensation of having a lump in their throat or feeling a foreign object caught in their throat. In some instances, globus is associated with reflux symptoms, and in others, with substantial anxiety. It is the linkage with anxiety that led to the older nomenclature “globus hystericus.” Unfortunately, studies have failed to define an objective anatomic or physiologic cause for globus, and we are left with the crucial data being in the history; globus sensation persists irrespective of the act of swallowing.

Evaluation

Once esophageal motility disorder is suspected in a patient, a series of investigations can be performed. There is no particular order in which they have to be performed; rather, it is the physician’s discretion, clinical experience and varies from case to case. Generally, similar to approaching any other illness, a non-invasive investigation is chosen.

Esophagraphy: An esophagography is usually chosen as a first investigation that shows the anatomical and physiological functioning of the esophagus.

In advanced achalasia, there may be a dilated intrathoracic esophagus with an air-fluid level. There may be a tapering of the esophagus at the lower esophagus, which gives a pathognomonic appearance of a “bird beak.” There may be normal anatomy in early achalasia, but the pooling of contrast will reflect the loss of peristalsis. In some instances, an epinephric diverticula may be noted immediately above the lower esophageal sphincter (LES).[10]

There is a 10 to 20% chance that these patients have a concurrent hiatal hernia in patients who have achalasia.

In DES, esophagogram may show the classic “corkscrew” or “rosary bead” appearance of the esophagus. Scleroderma esophagogram shows dilated esophagus, reflux, and weak or absent peristalsis.

Manometry

Integrated Relaxation: Average esophagogastric junction pressure for the 4 seconds of greatest relaxation within the 10-second period after a swallow. The normal value is up to 15mm Hg.

Distal Latency: The time taken for the swallow to reach the esophagogastric junction. Normal Value is up to 4.5 seconds.

Distal Contractile Integral: It is the measure of the strength of contraction of esophageal muscles. Normal value b/w 20 to 5000 mmHg/sec/cm.

• Achalasia: In patients with achalasia, manometry demonstrates hallmark findings of aperistalsis in the esophageal body and failure of the LES to relax.[11] In 90% of the cases, the diagnosis of achalasia can be made using these criteria, but in a small subset, approximately 10% of patients, the manometry is inconclusive due to the inability to place the catheter across LES correctly.
• Spastic Esophageal Motility disorders:
  • DES: It is characterized by normal peristalsis but simultaneous contractions of >30% of water swallows. Other associated findings include repetitive (>2 peaks), prolonged (>6 s), and high amplitude (>180mmHg) contractions. (Reproducibility of axial force and manometric recordings in the esophagus during wet and dry swallows.} it is also characterized by failure of LES to relax fully and abnormally high LES pressure (>40 mmHg).[12]
  • Nutcracker Esophagus: It has normal pattern peristalsis with high amplitude contractions >180mmHg with repetitive (>2 peaks), prolonged (>6 s) contractions, and high LES pressure (>40mmHg) on manometry.

Endoscopy

it is the first investigation in the setting of dysphagia. It is the only investigation tool that has both diagnostic and therapeutic significance while managing esophageal motility disorders. It may be inconclusive in early disease because gross abnormalities are usually appreciable later in the disease course.[13]

Stasis of food inside the esophageal lumen can be appreciated on endoscopy and may be seen as inflamed, eroded, ulcerated, erythematous, or friable mucosa. Biopsies can be taken at the time and be sent for histopathological diagnosis, or an endoscopic intervention is done simultaneously.

Treatment / Management

Patients with suspected esophageal motility disorders should be dealt with at a center with expert gastroenterology and surgical services.

• Medical care: The primary pathology in achalasia is irreversible and incurable; therefore, the mainstay of treatment is symptomatic control when the disease is mild to moderate.[14] From the intervention point of view, surgical and endoscopic therapies can also provide relief for a considerable amount of time.
  • Pharmacological interventions: With medicines, patients achieve good symptomatic control, particularly when the disease is in the early stages. Nitrates have been used historically, along with nifedipine, to control esophageal motility disorders. Other drugs used with limited efficacy are anticholinergics, theophylline, beta-2 agonists, phosphodiesterase inhibitors, and nitroglycerin. For predominant heartburn and reflux symptoms, gastroprokinetic and proton pump inhibitors (PPIs) are used. If an element of anxiety is also evident from history and clinical encounter, low-dose tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) are also used.
  • Endoscopic Therapy: Esophagogastroduodenoscopy (EGD) is performed, which can identify the exact anatomic site of narrowing. Dilation can be achieved with multiple techniques, but two widely used and comparatively less invasive techniques are:
    • Use of TTS pneumatic balloon
    • Use of EndoFlip dilation system

These can be done under general anesthesia or sedation and adequate analgesia. The patient may experience chest pain, worsening of heartburn, and reflux.

Another technique that can be employed while doing the EGD is the injection of botulinum toxin at the LES or at the site of narrowing. This is normally used for poor surgical candidates, or their disease is refractory to medical management.

• Surgical care: With the same principle as balloon dilatation, surgical interventions are targeted at the LES to release the high pressure at the esophagogastric junction (EGJ).[15] Three evidence-based surgical interventions are available for refractory or severe cases.[16] These procedures are:
  • Heller’s myotomy
  • Extended heller myotomy
  • Esophagectomy with gastric pull-up or intestinal interposition.

Differential Diagnosis

Differential diagnosis entirely depends on the presenting symptoms, but generally, when a patient presents with chest pain, a cardiac workup should be immediately done to rule out coronary artery disease. While suspecting esophageal motility disorders, the following differential diagnosis can be made and must be ruled out:

• Coronary artery disease (CAD)
• Chagas disease
• Pseudoachalasia
• Diffuse esophageal spasm
• Hypercontractile esophagus
• Xerostomia
• Globus sensation

The major objectives of history are to differentiate oropharyngeal dysphagia from esophageal dysphagia, xerostomia (hyposalivation), or globus sensation.

Globus sensation, in particular, is frequently confused with dysphagia. Unlike dysphagia, which occurs only during swallowing, globus sensation is prominent between swallows.

Patients relate the nearly constant sensation of having a lump in their throat or feeling a foreign object caught in their throat. In some instances, globus is associated with reflux symptoms, and in others, with substantial anxiety. It is the linkage with anxiety that led to the older nomenclature “globus hystericus.”

Unfortunately, studies have failed to define an objective anatomic or physiologic cause for globus, and we are left with the crucial data being the history; globus sensation persists regardless of the act of swallowing.

Prognosis

• Achalasia: It is a progressive disease, meaning that it requires chronic therapy and endoscopic or surgical intervention and reintervention. Patients may be required to be watchful about their dietary habits despite being on or after treatment.
• Scleroderma esophagus: The severity of the esophageal disease depends on how well the primary illness is well controlled. Since scleroderma is a progressive illness, patients present with significant acid reflux.
• Spastic esophageal disorders: Generally, it has a very favorable prognosis and patients usually attain good baseline status. Worsening usually warrants workup as these disorders have a propensity to develop into achalasia.

Complications

In patients suffering from achalasia, there is usually a higher risk of developing squamous cell carcinoma as compared to the general population but this has not been proven by sound scientific evidence. It is hypothesized that it is because of chronic mucosal irritation.

Deterrence and Patient Education

Patients should be counseled regarding the chronicity of this disease. They should have a detailed discussion with the clinician regarding therapeutic options, management outcomes, dietary and lifestyle modifications.

Enhancing Healthcare Team Outcomes

Important healthcare team members for patients with esophageal motility disorders include primary care providers, gastroenterologists, manometry nurses/techs, and surgeons. PCPs must help us in identifying patients that may be potentially suffering from dysphagia. Nurses and techs are trained to perform motility testing. Gastroenterologists and esophageal surgeons can interpret the results of testing and treat as an interprofessional team, depending on the outcome.