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Achalasia and Other Motor Disorders


The term esophageal motor disorder is commonly used to describe abnormal motility patterns demonstrated during esophageal manometry studies. Some of these disorders, such as esophageal achalasia, have well-defined abnormalities of esophageal motility, which correlate with clinical symptoms. However, other esophageal motility disorders have an abnormal contraction pattern on manometry, but their clinical significance is not always clear. The advent of high-resolution manometry (HRM) and the Chicago Classification criteria have improved our diagnostic capabilities and overall understanding of esophageal motility disorders. Because of the differences in the neuromuscular anatomy of the proximal and the distal esophagus, the illnesses affecting these regions also differ. We have therefore separated the motor disorders affecting the proximal and distal esophagus into two sections ( Box 22.1 ). Normal development, physiology, and motility of the esophagus are discussed in Chapter 1, Chapter 19 . In this chapter, we focus on specific esophageal motility disorders and discuss their clinical presentation, pathophysiology, diagnosis, and management.

BOX 22.1
Classification of Esophageal Motor Disorders

Disorders Affecting Proximal Esophagus

  • Primary

    • Cricopharyngeal achalasia

    • Cricopharyngeal incoordination

    • Cricopharyngeal hypotension

  • Secondary

    • Central nervous system:

    • Meningocele

    • Arnold-Chiari malformation

    • Cerebrovascular accidents

    • Multiple sclerosis

    • Autonomic nervous system:

    • Familial dysautonomia

    • Motor neurons

    • Bulbar poliomyelitis

    • Neuromuscular junction:

    • Myasthenia gravis

    • Botulism

    • Striated muscle:

    • Polymyositis

    • Dermatomyositis

    • Muscular dystrophy

Diseases Affecting Distal Esophagus

  • Primary

    • Achalasia

    • Diffuse esophageal spasm

    • Nutcracker esophagus

    • Nonspecific esophageal motility disorder

  • Secondary esophageal motility disorders

    • Gastroesophageal reflux

    • Hirschsprung disease

    • Intestinal pseudo-obstruction

    • Diabetes mellitus

    • Scleroderma and CREST syndrome

    • Inflammatory myopathies

    • Esophageal scarring

    • Tracheoesophageal fistula

    • Esophageal atresia

The development of solid-state manometry catheters with closely spaced sensors has allowed us to measure pressure from the pharynx to the gastroesophageal junction (GEJ) simultaneously. The recording is displaced as a Clouse plot, named after the pioneer, or as more commonly referred, high-resolution esophageal pressure topography or isobaric contour plots. Clouse plots are similar to the topographic charts used to show geographic elevation. Use of color allows for quicker interpretation of pressure, with cooler colors indicating low-pressure and warmer colors indicating high-pressure zones ( Fig. 22.1 , Table 22.1 ). The Chicago Classification (see Table 22.1 ) has standardized the diagnostic parameters for esophageal motility disorders in adults and improved interrater reliability. However, its application in younger, pediatric patients requires more evaluation. There is still a lack of normative data in children, in part because of changes in motility with the increase in length of the esophagus with age, poor patient cooperation leading to artifact, and changes in neurologic and developmental maturation of esophageal function. , Differences between the adult and pediatric parameters have not been elucidated. Furthermore, maturation of the peristaltic chain may continue through the toddler years. Even identifying complete swallows can be challenging based on work done by Staiano and colleagues, who showed that the first pressure segment is not always clearly discernible in young infants.

Fig. 22.1
This figure shows a high-resolution esophageal pressure topography chart of a normal esophageal swallow. The first thing one may notice are the two high pressure zones, the upper esophageal sphincter (UES) at the top of the panel and the lower esophageal sphincter (LES) gastric junction (EGJ) at the bottom of the panel. EGJ relaxation is measured as an accumulative lowest pressure over 4 seconds in a 10-second window and is referred to as the integrated relaxation pressure (IRP). As the patient commences a swallow, the upper esophageal sphincter relaxes and a normal propagating contraction can be seen. The break between the first part of peristalsis and the second signifies a transition zone (TZ) and indicates a change in control of peristalsis from the central nervous system to the enteric nervous system. The contractile deceleration point (CDP) is the transition from esophageal body to LES function. This denotes the highest deceleration of the contraction. Contractile front velocity (CFV) is a measure of the slope of the best-fit tangent prior to CDP. The distal latency (DL) is an important measure of propagation and is calculated by measuring time between UES relaxation and CDP. The area outlined by the dotted black box shows the distal contractile integral (DCI), which measures all pressure greater than 20 mm Hg. This is a marker of the vigor of the distal contraction. (See Tables 22.2 and 22.3 for normative data.)

TABLE 22.1
Esophageal Pressure Topography Metrics
Adapted from Gyawali CP, Bredenoord AJ, Conklin JL, et al. Evaluation of esophageal motor function in clinical practice. Neurogastroenterol Motil . 2013;25(2):99–133.
EPT Metric Definition Conventional Manometry Correlate
Integrated relaxation pressure (mm Hg) Lowest mean EGJ pressure for 4 contiguous or noncontiguous seconds of relaxation over a 10-s period (>15 mm Hg is abnormal). LES relaxation measured with best estimate position through the EGJ (>8 mm Hg is abnormal).
Peristaltic breaks (cm), peristaltic integrity Gap in the 20 mm Hg isobaric contour of the peristaltic contraction between the UES and EGJ, measured in axial length. Small defect: 2–5 cm in length. Large defect: 5 cm in length. Uses the 30 mm Hg amplitude at positions 3 and 8 cm above the LES to distinguish a swallow as ineffective (abnormal if <30 mm Hg).
DCI (mm Hg-s-cm) Amplitude-duration-length (mm Hg-s-cm) of the distal esophageal contraction greater than mm Hg from proximal to distal pressure troughs. Hypertensive: mean DCI of 10 swallows >5000. Hypercontractile: at least one swallow with a DCI >8000. Average of 10 swallows at two recording sites positioned 3 and 8 cm above the LES. Nutcracker >180 mm Hg. Revised definition >220–260 mm Hg.
Contractile front velocity (cm s −1 ) Slope of the tangent approximating the 30 mm Hg isobaric contour between the proximal pressure trough and the CDP (>9 cm s −1 ) is abnormal. Peristaltic progression from the UES to the LES at a rate of 2–8 cm s −1 ).
Distal latency (s) Interval between UES relaxation and the CDP (<4.5 s is abnormal). No correlate in conventional manometry.
CDP , Contractile deceleration point; DCI , distal contractile integral; EGJ , esophageal sphincter gastric junction; EPT , esophageal pressure topography; LES , lower esophageal sphincter; UES , upper esophageal sphincter.

Disorders of the Proximal Esophagus

Normal deglutition requires synchronized pharyngeal contraction, complete relaxation of the upper esophageal sphincter (UES) muscles, and traction by the neck muscles. This sequence of events pulls the larynx upward and forward, thereby opening the sphincter as the pharyngeal contractions propel the bolus through the sphincter. When the sequence is uncoordinated or the UES sphincter fails to relax, the bolus is mishandled. Disorders affecting the UES are usually part of a generalized neurodevelopmental problem, and oral and pharyngeal phases of swallowing may also be affected.

Upper Esophageal Sphincter Achalasia

Primary cricopharyngeal achalasia usually presents soon after birth, with choking and coughing during feeds, nasal regurgitation of feeds, tracheal aspiration and dysphagia, cyanosis, and failure to thrive. Diagnosis is often delayed because of the rarity of the disorder. A prominent posterior indentation (cricopharyngeal bar) is usually identified on a lateral radiograph in the pharyngoesophageal segment during a contrast swallow study, but this may be more difficult to identify in infants and children. A dilated pharynx, lack of transit through the UES, a to-and-fro movement of contrast in the pharynx, aspiration, and nasal reflux are often observed during videofluoroscopic swallow studies. In older children, the administration of varying food bolus consistencies, rather than just liquid contrast, can help to evaluate the swallowing mechanism in detail. Similar findings can be observed in children with more generalized neuromuscular disorders who do not initiate a coordinated pharyngeal swallow response on bolus entry into the pharynx. This can lead to the inappropriate diagnosis of cricopharyngeal achalasia by less experienced clinicians.

Manometric studies can confirm incomplete relaxation of the UES in some patients with radiographic abnormalities. However, there is often a discrepancy between radiographic and manometric findings. This could be partly due to the inherent difficulty in performing manometric studies in this region, especially in an uncooperative infant. Maintaining the position of the transducers in the UES during swallowing can be difficult. It is imperative to recognize that a prominent cricopharyngeal muscle during radiographic studies can be seen in normal infants, and it has been observed in up to 5% of adults having barium swallow studies for various reasons who did not have cricopharyngeal achalasia.

Several neuromuscular disorders have been associated with cricopharyngeal achalasia ( Box 22.2 ). In Chiari malformation, swallowing difficulty usually predates other signs of brainstem compromise. Associated esophageal motility abnormalities, such as spontaneous esophageal contractions and nonpropagation of swallows, are also present. In most patients, normal swallowing is observed following craniocervical decompression surgery. Severity of the preoperative brainstem dysfunction is a good predictor of outcome following surgery.

BOX 22.2
Conditions Associated With Cricopharyngeal Dysfunction

  • Myoneural junction defect

    • Myasthenia gravis

  • Muscular abnormality

    • Dermatomyositis and polymyositis

    • Systemic lupus erythematosus

    • Muscular dystrophy

    • Acrosclerosis

    • Thyrotoxic myopathy

    • Paroxysmal hemoglobinuria

    • Werdnig-Hoffmann disease

    • Tetanus

  • Neural defect

    • Arnold-Chiari malformation

    • Cerebral palsy

    • Amyotrophic lateral sclerosis

    • Syringobulbia

    • Poliomyelitis

    • Posterior inferior cerebellar artery syndrome

    • Prematurity

    • Meningomyelocele and hydrocephalus

  • Others

    • Down syndrome

Symptoms of UES achalasia can spontaneously improve in some children; therefore an initial conservative approach with aggressive pulmonary and nutritional support can be tried. However, one must be vigilant and aware of the risk of aspiration, which can be life threatening. When spontaneous recovery does not occur, dilation, surgical or endoscopic cricopharyngeal myotomy should be considered. A single dilation may be sufficient and is effective in babies as young as 5 months of age. Botox injections have been shown to be effective for patients with incomplete relaxation after dilation or as primary therapy. An adult study of radiographic and manometrically diagnosed patients with cricopharyngeal achalasia showed that cricopharyngeal myotomy was more beneficial when high pharyngeal pressures could be generated during swallows. This suggests that when pharyngeal constrictors were able to generate contractions, the pharyngoesophageal bolus transit improved when the obstruction by the contracted UES was relieved.

Cricopharyngeal Incoordination

The pharynx receives frequent stimulation during breathing, bolus oral feeding, and gastroesophageal reflux (GER). Depending on the type of stimulus, various reflex mechanisms help to adapt the anatomy and physiology of this region. This allows passage of the contents into the respiratory or the gastrointestinal tract. Cricopharyngeal incoordination is characterized by a delay in pharyngeal contraction in relation to cricopharyngeal relaxation during bolus oral feeding. It presents with swallowing difficulties, choking, and aspiration. Neonates with “transient cricopharyngeal incoordination” have a normal suck but have repeated choking and aspiration episodes. These symptoms can be easily confused with tracheoesophageal fistula or laryngotracheoesophageal cleft. Repeated choking and aspiration episodes can be life threatening, and early diagnosis is important. The clinical course is variable, and spontaneous improvement has been reported. Nutritional support and feeding advice are essential. The aim should be to minimize the risk of aspiration.

Cricopharyngeal incoordination has also been reported in patients with central nervous system dysfunction such as Chiari malformation. Cricopharyngeal incoordination may also result from cervical inflammation and constrictive processes, which restrict laryngeal and hyoid bone movement. In Pierre Robin sequence, sucking-swallowing electromyography and esophageal manometry reveal dysfunction in the motor organization of the tongue, the pharynx, and the esophagus. Patients with familial dysautonomia (Riley-Day syndrome) have delayed but complete relaxation of UES and associated esophageal motility disorders. Wyllie and colleagues reported two children with drooling following nitrazepam use; both had delayed relaxation of the UES in relation to pharyngeal contractions. Cricopharyngeal incoordination with high-peaked esophageal peristalsis was reported in four patients with resistant myoclonic epilepsy being treated with nitrazepam. One patient required ventilation and improved following discontinuation of nitrazepam therapy. UES dysfunction has also been reported in patients with Russell-Silver syndrome, chromosome 5p deletion (or cri du chat) syndrome, and minimal change myopathy.

Upper Esophageal Sphincter Hypotension

Reduced UES resting pressure is seen in a variety of neuromuscular disorders ( Box 22.3 ). It is a manometric diagnosis, but the clinical significance is not clear because the UES is completely relaxed during sleep. It may predispose to regurgitation of esophageal contents into the oropharynx and risk of aspiration into the respiratory tract.

BOX 22.3
Factors Influencing Upper Esophageal Sphincter Pressure

Reduced Upper Esophageal Sphincter Pressure

  • Sleep

  • Belching

  • Expiration

  • Vomiting

  • Neuromuscular disorders

    • Myasthenia gravis

    • Polymyositis

    • Oculopharyngeal muscular dystrophy

    • Amyotrophic lateral sclerosis

Increased Upper Esophageal Sphincter Pressure

  • Stress

  • Esophageal distension

  • Intraesophageal acid

  • Pharyngeal stimulation with air or water

  • Inspiration

Disorders of the Distal Esophagus

Esophageal Achalasia

Incidence and Heredity

Achalasia is a motor disorder of the esophagus characterized by loss of esophageal peristalsis, increased lower esophageal sphincter (LES) pressure, and absent or incomplete relaxation of the LES with swallows. An epidemiologic study in the United Kingdom reported an incidence of 0.18/100,000 children/year, which suggests a potential rise in the incidence rates. Patients with achalasia can present at any time from birth to the ninth decade of life. The majority of these are sporadic patients, and it is estimated that familial achalasia represents less than 1% of all achalasia cases. Most of these are horizontally transmitted and present in the first 5 years of life. Familial achalasia is more common in children born of consanguineous relationships, suggesting an autosomal recessive inheritance.

The clinical presentation depends on the duration of the disease and age of the child. The onset is usually gradual, and there can be a considerable delay from the time of onset of symptoms to diagnosis. In a review of 12 published studies, the mean duration of symptoms before the diagnosis was established was 23 months. The mean age at diagnosis was 8.8 years. In a worldwide survey of 175 children with achalasia, only 6% of the patients presented during infancy. The youngest reported patient was a 900-g, 14-day-old premature infant.

Infants and toddlers present with choking, cough, recurrent chest infections, feeding aversion, and failure to thrive. Older children usually present with vomiting, dysphagia, weight loss, respiratory symptoms, and slow eating ( Table 22.2 ). Dysphagia may initially be confined to solids but usually progresses to involve both liquids and solids. Stress is known to aggravate the symptoms. The child usually complains of food getting stuck in the chest, and repeated attempts at swallowing or washing the food down with liquid helps to relieve the symptom. Because of swallowing difficulty and discomfort, the oral intake may be reduced and lead to weight loss. Once the esophagus is dilated, the patient may regurgitate undigested, nonbilious, and generally nonacidic food eaten hours or days earlier. A large quantity of saliva can accumulate, especially at night, when the patient is lying flat. Early morning waking with choking episodes, bouts of coughing due to aspiration of esophageal contents, and vomiting whitish frothy saliva may be reported. Sudden death from aspiration is a serious risk. The patient may be aware of the gurgling sound from the fluid sloshing in the dilated esophagus.

TABLE 22.2
Symptoms of Achalasia in Children
Symptom % of Children
Vomiting 80
Dysphagia 76
Weight loss 61
Respiratory symptoms 44
Chest pain/odynophagia 38
Failure to thrive 31
Nocturnal regurgitation 21

Pathogenesis

Infectious and environmental causes have been implicated in studies of idiopathic achalasia, but most evidence points to an autoimmune phenomenon. The proposed mechanism includes a potential viral trigger in a genetically susceptible individual. Human leukocyte antigen (HLA) genotype DQA1∗ 0103 and DQB1∗ 0603 alleles have been identified in patients with achalasia. An aberrant autoimmune response may be responsible for the loss of myenteric neurons. Cytotoxic CD8 T cells are the predominant inflammatory component to cause the sustained inflammation, but eosinophils, plasma cells, B cells, mast cells, and rare macrophages can be seen in esophageal tissues of resected specimens. In addition, it has been suggested that infectious or toxic inflammatory processes trigger interferon-γ (IFNγ) release, thereby inducing the class II antigen expression on neural tissue. Neural tissue expressing class II antigen is recognized as foreign by the T lymphocytes. Serum antibodies to neurons of the myenteric plexus in patients with achalasia have been reported but may be more of a consequence rather than the cause of the disease. , There may be minimal esophageal dilation in early stages of the disease, and full-thickness esophageal biopsies show inflammation of the myenteric plexus, without a decrease in ganglion cells. Later, there is a reduction in the ganglion cell number and a decrease in varicose nerve fibers in the myenteric plexus ; this may signify a progression of type II achalasia to type I. In type III achalasia, ganglion cells are preserved even late into the disease process, indicating a potentially different pathophysiologic event. Human studies have demonstrated the absence of neuronal nitric oxide synthase (NOS) in the LES of patients with achalasia, and physiologic studies showed LES relaxation when nitric oxide (NO) was added to the muscle strips. , Degenerative changes in the vagus nerve have also been reported. Quantitative and qualitative changes in the dorsal motor nucleus of the vagus and a decrease in vasoactive intestinal peptide (VIP) and neuropeptide Y have been implicated, as well as choline acetyltransferase imbalance. ,

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