Conventional manometry 
Distal esophageal spasm
>10% simultaneous contractions
• Intermittent normal peristalsis
• Spontaneous contractions
• Repetitive contractions
• Multi-peaked contractions
Elevated mean distal wave amplitude
High-resolution manometry 
Distal esophageal spasm
≥20% premature (abnormal distal latency) contractions
• Some normal peristalsis may be present
Hypercontractile (“jackhammer”) esophagus
≥20% Hypercontractile (elevated distal contractile integral) swallows
• Multi-peaked contractions
• Can co-occur with an EGJ outflow obstruction, if not meeting criteria for an achalasia subtype
Esophageal symptoms, including chest pain, can be nonspecific when it comes to identifying the underlying pathology. Therefore, an initial evaluation should include a careful upper endoscopy to evaluate for a potential mechanical obstruction (e.g., stricture, hiatal hernia), as well as esophageal biopsies to evaluate for eosinophilic esophagitis (especially with coexisting dysphagia). Supplementary imaging, such as barium esophagram, may also be helpful to exclude an esophageal mechanical obstruction and may provide suggestive evidence for a spastic motility disorder, i.e., tertiary contractions, or rarely a corkscrew appearance [8, 9]. Additionally, gastroesophageal reflux disease is a common cause of esophageal chest pain and thus empiric trial of reflux therapy (i.e., proton pump inhibitor, PPI) or objective testing for reflux (esophageal pH testing) should be considered .
Esophageal manometry is the primary test to establish a diagnosis of a spastic esophageal motility disorder [5, 7]. Achalasia (particularly spastic, vigorous, or type III achalasia) could be considered within a spectrum of spastic motility disorders and may share some clinical features, such as an association with esophageal chest pain. Nonetheless, the spastic motility disorders described in the remainder of this chapter (DES, nutcracker esophagus, and jackhammer) should be considered differentiated from achalasia primarily based on normal deglutitive lower esophageal sphincter (LES) pressures on manometry.
With conventional, line-tracing manometry, simultaneous contraction (often defined by a rapid propagation velocity) was the typical diagnostic criterion for DES (Fig. 2.1) though (a) repetitive, (b) multi-peaked, (c) high-amplitude, (d) prolonged-duration, or (e) spontaneous contractions, in addition to required intermittent normal peristalsis, were also occasionally incorporated [3, 5]. Some overlap can be appreciated with the criteria for nutcracker esophagus, which is characterized by high-amplitude contractions, but also sometimes repetitive or long-duration contractions .
Spastic esophageal motility disorders. Conventional line tracings (left) and high-resolution manometry/esophageal pressure topography (EPT; center) of the same swallow as well as a barium esophagram (right) from patients with (a) distal esophageal spasm (DES) and (b) jackhammer esophagus are displayed. Deglutitive esophagogastric junction pressures were normal (residual pressure < 8 mm Hg; integrated relaxation pressure, IRP, <15 mm Hg) in both cases. (a) DES is diagnosed on line tracings by simultaneous contractions (blue box); the abnormal, reduced distal latency (DL < 4.5 s), indicating a premature contraction, can be appreciated on the EPT. The corkscrew appearance of the esophagus is apparent on the esophagram. (b) Jackhammer esophagus is diagnosed based upon the elevated distal contractile integral (DCI > 8000 mm Hg s cm) on EPT. On the line tracings, the repetitive, high-amplitude, simultaneous contractions could be classified as DES. The esophagram in this patient was normal. Figure used with permission from the Esophageal Center at Northwestern
More recently, high-resolution manometry (HRM) and associated esophageal pressure topography (EPT) have provided enhanced depiction of esophageal motility characteristics and subsequently revised concepts (and subsequently diagnostic criteria) for esophageal motility disorders. Thus, utilizing the improved spatial resolution of HRM, rapidly propagating (simultaneous) esophageal contractions were identified as a nonspecific finding often found in patients with otherwise weak or normal peristalsis . Alternatively, premature swallows, which were defined by a reduced distal latency (the time interval from the onset of swallow to the contractile deceleration point, i.e., end of the fast component of esophageal peristalsis, Fig. 2.1) appeared to represent a distinct pathophysiologic manifestation of abnormal inhibitory innervation [11, 12] and now entail a chief criterion for DES.
Additionally, contractile vigor can be assessed with HRM as a composite measure of pressure amplitude (mm Hg) × contraction duration (s) × contractile length (cm): the distal contractile integral (DCI). Thus, the extreme clinical phenotype of esophageal hypercontractility is defined by swallows of a greater vigor (as defined by elevated DCI) than those observed in asymptomatic controls [7, 13]. Sometimes associated with repetitive or multi-peaked contractions this motility pattern was termed jackhammer esophagus ; thus, it appears possible that this entity may have been represented in former studies describing DES by repetitive, high-amplitude, repetitive and/or long-duration contractions on conventional manometry .
It is worth noting that studies that described DES or nutcracker esophagus using conventional manometry with a single LES pressure sensor (i.e., without the use of an LES pressure sleeve, which was most of them) were susceptible to misidentifying achalasia patients due to the manometric measurement phenomenon known as LES “pseudorelaxation ” (Fig. 2.2): the erroneous but apparent decrease in “LES” pressure related to proximal migration of the LES during swallow-associated esophageal shortening, which can be profound in patients with achalasia.
Lower esophageal sphincter “pseudorelaxation.” Conventional, line-tracing manometry (a) and high-resolution manometry/esophageal pressure topography (EPT), with overlaid line tracings (b), of a patient with achalasia. The line tracing (a) could be interpreted as distal esophageal spasm based on the simultaneous, repetitive esophageal contractions (blue boxes) with normal lower esophageal sphincter (LES) relaxation pressure. However, on EPT (b), the pan-esophageal pressurization and abnormal deglutitive LES pressure (integrated relaxation pressure, IRP, >15 mm Hg) can be easily appreciated. The swallow-associated esophageal shortening pulled the LES proximal to the single LES pressure sensor and resulted in “pseudorelaxation” of the LES. Figure used with permission from the Esophageal Center at Northwestern
Finally, while the diagnosis of spastic motility disorders is typically defined by stationary esophageal manometry, symptom-associated or abnormal spastic esophageal contractions may occur infrequently and thus outside a 10–15 swallow manometry study. Consequently, an increased diagnostic yield has been reported for DES by increasing the manometric testing period, and even prolonged, ambulatory manometry (Fig. 2.3) [14–16]. A recent study evaluating stationary HRM and 24-h ambulatory manometry with pH impedance identified esophageal spasm (symptom-associated, simultaneous, and often multi-peaked or repetitive contractions of at least >100 mm Hg and lasting at least 3 s) on ambulatory manometry in 7% (4/59) of patients . None of the 59 patients met the diagnostic criteria for a spastic motility disorder on stationary HRM, though three of the four patients with DES on ambulatory manometry had subtle contractile abnormalities on stationary HRM. However, patient tolerance to prolonged manometry catheter placement and limited availability remain limitations of utilizing ambulatory manometry in typical clinical practice.
Symptom association with manometric findings. (a) Four representative swallows (white arrows), three failed and one weak, from the standard ten-swallow high-resolution manometry (HRM) study protocol from a patient evaluated for severe episodic chest pain with rare dysphagia. The esophageal motility diagnosis was ineffective esophageal motility. (b) During prolongation of the HRM recording for 2 h, multiple episodes of chest pain occurred that were associated with repetitive, vigorous contractions associated with esophageal shortening; the purple boxes indicate when chest pain was present. Figure used with permission from the Esophageal Center at Northwestern. DCI distal contractile integral, IRP integrated relaxation pressure
Epidemiology of Esophageal Spasm
Noncardiac chest pain, often attributed to chest pain of an esophageal origin, is a common entity with an approximately 13% worldwide prevalence . The majority of esophageal chest pain is related to gastroesophageal reflux or functional chest pain [1, 2]. On the other hand, primary manometric diagnoses of spastic esophageal motility disorders make up only a small proportion of noncardiac chest pain patients, though information regarding the epidemiology of spastic esophageal motility disorders relates to the diagnostic criteria applied, and thus may fluctuate over the course of evolving diagnostics definitions.
Using conventional manometry criteria, a recent study of 350 consecutive patients undergoing manometry from 2012 to 2013 found DES (defined by simultaneous contractions) in 3% and nutcracker esophagus (defined by mean distal wave amplitude >220 mm Hg) in 3% . As a reference, achalasia, which has an estimated incidence rate of about 1/100,000 person-years, was found in 8% of the 350 patients [18, 19].
With HRM evaluation and criteria, DES with premature contractions (reduced distal latency) in ≥20% of swallows was found in 0.5% (n = 6) of 1070 patients without previous foregut surgery . Among the same HRM cohort, 44/1070 (4.1%) had at least one hypercontractile (DCI > 8000 mm Hg s cm) swallow;  thus under the current HRM diagnostic criteria requiring ≥20% of hypercontractile swallows, hypercontractile esophagus would be expected to be diagnosed even more infrequently . Again for reference, incident achalasia was diagnosed in 99/1000 (10%) of consecutive HRMs from the same center .
Therefore, spastic esophageal motility disorders ultimately reflect rare disorders encompassing even a small portion (<5%) of all patients undergoing esophageal manometry. Reports of higher rates should raise questions about diagnostic interpretation (particularly with DES and correct identification of the contractile deceleration point and subsequent measurement of the distal latency).
The pathophysiologic mechanism(s) behind spastic or hypercontractile esophageal motility disorders remain incompletely understood though multiple hypotheses have been suggested. In addition to esophageal neuromuscular dysfunction or imbalance, associations of spastic motility disorders to esophageal obstruction or gastroesophageal reflux are reported. Thus a fundamental question is posed when spastic manometric features are identified: primary esophageal motility disorder or secondary response to another (potentially subtle) esophageal stimuli?
Neuromuscular dysregulation is thought to be the pathologic foundation of primary esophageal motility disorders (e.g., achalasia) and is also hypothesized to be a pathologic mechanism of DES and hypercontractile esophageal disorders. Impaired inhibitory innervation among patients with simultaneous contractions (DES) was supported by an elegant study demonstrating abnormalities of distal contractile latency and in the expected deglutitive inhibition with paired swallows . Further, spontaneous contractions were induced by cholinergic (excitatory) stimulation in both DES and patients with normal motility and spontaneous contractions were inhibited by cholinergic blockade in DES patients . Another study evaluating esophageal muscle specimens of patients with nutcracker esophagus found an increased ratio of cholinergic (excitatory) to nitronergic (inhibitory) protein immunostaining compared with patients with normal manometries, thus supporting a role of neural signaling imbalance within nutcracker esophagus as well . However, another study evaluating esophagectomy specimens for refractory esophageal chest pain found normal esophageal ganglion among patients with DES (n = 2) and nutcracker esophagus (n = 4) .
Abnormal muscular function has also been proposed as a pathologic mechanism in spastic motility disorders. Thickened circular esophageal muscle has been observed in patients with DES, nutcracker, and jackhammer esophagus [23, 24]. Additionally, asynchrony between circular and longitudinal muscle contraction was reported in patients with nutcracker esophagus using a sophisticated simultaneous manometry with high-frequency intraluminal ultrasound technique ; further, this muscular asynchrony was able to be induced with cholinergic stimulation (edrophonium) and reversed with cholinergic inhibition (atropine). Therefore, a contribution of reduced esophageal inhibitory and/or excess excitatory innervation appears to be related to the underlying mechanism of spastic motility disorders.
Additionally, simultaneous, repetitive, and hypertensive esophageal contractions have been reported in both animal models and humans with esophageal obstruction. In cats and opossum, simultaneous, repetitive, multi-peaked, and increased wave amplitude contractions were induced following creation of a distal esophageal obstruction [26–28]. In humans, an intriguing study utilizing HRM on patients with laparoscopic adjustable gastric bands (LABG) reported inducing repetitive and hypertensive contractions when inducing an esophageal obstruction by overfilling the gastric band .
The association of spastic motility features with reflux has also been reported. Objective evidence of reflux (esophagitis or abnormal esophageal pH testing) or a symptomatic response to reflux-targeted therapy (PPI or fundoplication) was reported among patients with DES, nutcracker, and jackhammer esophagus [13, 30, 31]. Further, a previous study utilizing combined manometry and acid perfusion reported provocation of chest pain and spastic motility patterns (simultaneous and repetitive contractions) among patients with a normal manometry at baseline . Thus, the demonstration that the typical manometric features of spastic motility disorders can be induced by esophageal obstruction and esophageal acid exposure supports the notion that these spastic manometric features can also represent a secondary esophageal response.
Beyond the mechanisms behind spastic esophageal contractions, the generation of symptoms, particularly chest pain, among these spastic motility disorders also remains incompletely understood, particularly as esophageal symptoms are not consistently associated with objectively measured abnormal esophageal contractions . Esophageal tissue ischemia was proposed as a mechanism of symptom generation based on a sophisticated study that demonstrated reduced esophageal wall blood perfusion in patients with nutcracker esophagus compared with asymptomatic controls ; further, controls had an increase in esophageal blood perfusion during meals which appeared to be blunted in the nutcracker patients.
Esophageal hypersensitivity also appears to be a contributing factor to symptom generation. Patients with nutcracker esophageal showed a lower pain threshold to intraesophageal balloon distension than in healthy controls . Additionally, symptomatic improvement without changes in spastic manometric findings following therapy with trazodone, an antidepressant without effects on esophageal motor function (e.g., anticholinergic properties), supports a component of hypersensitivity .
Ultimately, the mechanisms behind spastic and hypertensive esophageal contractions are complex and likely multifactorial. Therefore multimodal management strategies may need to be applied.
Patient question: How is esophageal spasm treated?
Suggested response to the patient:
The treatment of esophageal spasm typically targets the abnormal esophageal contractions, and thus begins with medications to relax the esophageal muscles. However, esophageal targeted smooth muscle relaxants are limited; thus the medications are used off-label for esophageal symptoms. Therefore the symptomatic benefits need to be gauged against potential side effects, such as lightheadedness and drops in blood pressure. Sometimes injection of botulinum toxin or esophageal surgery is used to diminish the abnormal esophageal contractions. However, given the association of these spastic motility disorders with other causes, for example esophageal obstruction or even esophageal hypersensitivity, further diagnostic evaluation, a trial of esophageal dilation with endoscopy, or trials of medications to treat esophageal sensitivity (antidepressants) might be considered before pursuing more aggressive endoscopic or surgical therapy .
Treatment of Spastic Esophageal Motility Disorders
Following a thorough diagnostic evaluation and consideration for empiric treatment trials, e.g., acid suppression or even empiric dilation, given the potential for an alternate (or secondary) cause of esophageal symptoms and manometric findings, the treatment of primary spastic esophageal motility disorders aims to reduce the spastic or vigorous esophageal contractions. Multiple pharmacologic, endoscopic, or surgical therapies (Table 2.2) are available; thus the typical approach should be to start with less invasive options (i.e., medical therapy) and reserve more invasive endoscopic or surgical approaches for patients with medical-refractory and severely life-altering symptoms. It is worth noting that the majority of clinical studies reported have included only patients defined by conventional manometry criteria; thus generalization of these reports to HRM-defined spastic motility disorders carries potential limitations.
Therapeutic options for spastic esophageal motility disorders
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