Residency · Residency · Gastroenterology

Esophageal Motility Disorders and Achalasia

Introduction and Classification

Chicago Classification v4.0 (2021)

The Chicago Classification version 4.0, published in 2021, represents the most current and comprehensive hierarchical analysis scheme for interpreting high-resolution manometry (HRM) studies. This classification system organizes esophageal motility disorders into a structured diagnostic hierarchy that mandates systematic evaluation of key manometric parameters before arriving at a final diagnosis.

At the top of the diagnostic hierarchy are the disorders of esophagogastric junction (EGJ) outflow, which include the three subtypes of achalasia (types I, II, and III) and EGJ outflow obstruction (EGJOO). The major disorders of peristalsis constitute the next tier and encompass absent contractility, distal esophageal spasm (DES), and hypercontractile esophagus, also known as jackhammer esophagus. Below these are the minor disorders of peristalsis, which include ineffective esophageal motility (IEM) and fragmented peristalsis. Importantly, the Chicago Classification v4.0 acknowledges the existence of normal motility variants and explicitly requires clinical correlation before diagnosing any minor disorder of peristalsis, as manometric findings alone may not be clinically significant.

Manometric Landmarks and Key Metrics

Several key metrics form the foundation of HRM interpretation. The integrated relaxation pressure (IRP) is defined as the median of the 4-second lowest pressure values recorded during the deglutitive relaxation window, and it serves as the primary measure of EGJ relaxation. The upper limit of normal for IRP varies by equipment manufacturer: 15 mmHg for Medtronic systems and 12 mmHg for Diversatek systems. The distal contractile integral (DCI) quantifies the vigor of esophageal peristalsis by measuring the amplitude, duration, and length of the contraction exceeding 100 mmHg from the transition zone to the proximal margin of the EGJ. Normal DCI values range from 450 to 8000 mmHg-s-cm. The distal latency (DL) measures the interval from upper esophageal sphincter relaxation to the contractile deceleration point and is considered normal when it exceeds 4.5 seconds. For fragmented peristalsis, the key parameter is a break size exceeding 5 cm in the 20 mmHg isobaric contour.

Achalasia

Pathophysiology

The fundamental pathophysiologic event in achalasia is the selective loss of inhibitory ganglion cells within the myenteric (Auerbach) plexus of the esophageal wall. This loss specifically affects neurons that produce nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP), the key mediators of smooth muscle relaxation and coordinated peristalsis. In the early stages of disease, the cholinergic excitatory neurons remain relatively preserved, creating an imbalance that favors unopposed contractile tone at the lower esophageal sphincter.

Histopathologic examination of the myenteric plexus reveals an inflammatory infiltrate composed predominantly of CD3-positive T lymphocytes, strongly suggesting an autoimmune etiology. This concept is further supported by the association of achalasia with HLA-DQw1 and by the hypothesis that viral triggers, including herpes simplex virus type 1 (HSV-1) and measles virus, may initiate the autoimmune cascade through molecular mimicry. The end result of this inflammatory destruction is impaired LES relaxation coupled with absent or abnormal esophageal peristalsis.

Subtypes (Chicago Classification)

The Chicago Classification recognizes three distinct subtypes of achalasia, each with unique manometric signatures and clinical implications for treatment response.

Type I achalasia, also referred to as classic achalasia, is characterized by an elevated median IRP with 100% failed peristalsis, defined as all swallows having a DCI below 100 mmHg-s-cm. There is no esophageal pressurization observed during swallows. Patients with type I achalasia often present with a dilated, sigmoid-shaped esophagus on imaging, reflecting long-standing disease with progressive esophageal decompensation.

Type II achalasia, described as achalasia with esophageal compression, also demonstrates an elevated median IRP and 100% failed peristalsis. However, the distinguishing feature is the presence of panesophageal pressurization in more than 20% of swallows, indicating simultaneous contraction of the esophageal longitudinal muscle. Type II achalasia has the best treatment response among all subtypes, with success rates approaching 96% following either peroral endoscopic myotomy (POEM) or Heller myotomy.

Type III achalasia, the spastic variant, features an elevated median IRP with no normal peristalsis and the presence of premature (spastic) contractions with a distal latency below 4.5 seconds in more than 20% of swallows. This subtype has the worst treatment response among the three and may demonstrate clinical and manometric overlap with distal esophageal spasm.

<image>A detailed high-resolution manometry (HRM) Clouse plot comparison showing three panels side by side labeled "Type I," "Type II," and "Type III" achalasia. Each panel should display the characteristic pressure topography from UES to LES over a 10-second swallow window. Type I shows absent peristalsis with no pressurization and elevated IRP at the LES. Type II shows panesophageal pressurization as a uniform band of green-yellow color across the esophageal body with elevated IRP. Type III shows premature spastic contractions with shortened distal latency and elevated IRP. Use a standard HRM color scale: blue for low pressure, green for moderate, yellow-red for high pressure. Label UES, LES, transition zone, and IRP measurement window on each panel. Include DCI and IRP values for each subtype.</image>

Clinical Presentation

The hallmark symptom of achalasia is progressive dysphagia to both solids and liquids simultaneously, a feature that distinguishes it from mechanical causes of obstruction, which typically produce dysphagia to solids before liquids. Patients frequently report regurgitation of undigested food that has been retained in the dilated esophagus, and this often occurs in the nocturnal position, raising the risk for aspiration events. Chest pain is a prominent symptom, particularly in patients with type III achalasia, and weight loss may accompany advanced disease.

Aspiration pneumonia represents a serious complication in patients with advanced disease and significant esophageal dilation. Clinicians must maintain a high index of suspicion for pseudoachalasia, particularly in patients presenting with red flag features: age over 55 years, rapid symptom onset occurring over fewer than 6 months, and significant weight loss exceeding 15 pounds. Pseudoachalasia must prompt thorough evaluation to exclude malignancy, most commonly adenocarcinoma of the gastric cardia or fundus, and less frequently pancreatic cancer.

Diagnostic Workup

The diagnostic evaluation of suspected achalasia involves multiple complementary modalities. Upper endoscopy (EGD) may reveal a dilated esophagus with retained food and saliva, a puckered appearance of the LES known as the "rosette" sign, and resistance when traversing the gastroesophageal junction. Importantly, endoscopy must include retroflexion examination with biopsies to rule out pseudoachalasia from an infiltrating submucosal neoplasm.

Barium esophagram demonstrates the classic "bird's beak" tapering at the gastroesophageal junction, a dilated esophageal body, and absent primary peristalsis, often with an air-fluid level. The timed barium swallow (TBS) using 200 mL of barium with imaging at 1, 2, and 5 minutes provides a quantitative assessment of esophageal emptying, as the height of the barium column correlates with treatment response and is the best objective measure for post-treatment follow-up.

High-resolution manometry is the gold standard for both diagnosis and subtyping of achalasia. When pseudoachalasia is suspected, endoscopic ultrasound and CT of the chest and abdomen should be performed to exclude malignancy or other infiltrative processes at the gastroesophageal junction.

Treatment Options

Pharmacologic therapy serves only as a temporizing measure in patients who are not candidates for definitive intervention. Sublingual nifedipine at 10 to 30 mg or isosorbide dinitrate at 5 to 10 mg administered before meals provides limited efficacy, with only 30 to 40% symptom reduction, and is associated with significant side effects including headache and hypotension.

Botulinum toxin injection, delivered as 100 units divided into 4 quadrants at the LES, is effective in 60 to 80% of patients at 1 month but demonstrates diminishing returns over time, with fewer than 40% maintaining response at 12 months. This approach is best reserved for patients who are poor surgical or procedural candidates.

Pneumatic dilation (PD) employs graded Rigiflex balloons of 30, 33, and 35 mm diameter. The standard approach begins with a 30 mm balloon and escalates to larger diameters if symptom relief is insufficient. Perforation risk ranges from 1 to 5%, and efficacy varies between 50 and 93% depending on follow-up duration. The landmark European Achalasia Trial demonstrated non-inferiority of graded pneumatic dilation to laparoscopic Heller myotomy at 5-year follow-up.

Laparoscopic Heller myotomy (LHM) involves a 6 to 8 cm esophageal myotomy extending 2 to 3 cm onto the gastric cardia, coupled with a partial fundoplication to prevent post-myotomy reflux. The Dor anterior partial fundoplication is generally preferred. Success rates range from 85 to 95% at 5 years, with gastroesophageal reflux occurring in 10 to 30% of patients when fundoplication is omitted.

Peroral endoscopic myotomy (POEM) utilizes a submucosal tunnel technique to perform an anterior or posterior myotomy and can be extended proximally for type III achalasia to address the spastic esophageal segment. Success rates are 90 to 98% at 2 years. However, POEM is associated with higher rates of gastroesophageal reflux disease (40-60%) compared to LHM due to the absence of a concurrent anti-reflux procedure. Proton pump inhibitor therapy is required for all patients after POEM.

<image>A step-by-step procedural illustration of POEM (peroral endoscopic myotomy) in 6 panels arranged in a 2x3 grid. Panel 1: Mucosal incision at approximately 10 cm proximal to GEJ, showing submucosal injection with methylene blue-tinted saline creating a bleb. Panel 2: Submucosal tunneling with dissection plane clearly visible between mucosa (labeled, pink) and muscularis propria (labeled, red-brown). Panel 3: Long submucosal tunnel extending past GEJ with transparent cap at scope tip visible. Panel 4: Selective myotomy of circular muscle fibers with longitudinal fibers preserved, labeled distinctly. Panel 5: Extension of myotomy 2-3 cm past GEJ onto gastric cardia. Panel 6: Closure of mucosal entry with endoscopic clips. Use anatomical cross-section insets showing the layers (mucosa, submucosa, circular muscle, longitudinal muscle, serosa) in Panels 2 and 4. Label all structures clearly with leader lines.</image>

Treatment Selection by Subtype

Treatment selection should be guided by achalasia subtype, as this is the strongest predictor of treatment response. For type I achalasia, pneumatic dilation, LHM, and POEM are all effective modalities, although PD may have slightly lower long-term success rates in younger patients. Type II achalasia is the best responder to all therapeutic modalities, and POEM or LHM are generally preferred. Type III achalasia is best addressed by POEM, which allows for a longer myotomy that can be extended to the proximal spastic segment, whereas LHM is less effective due to its limited ability to extend the myotomy proximally through the chest. For patients with end-stage sigmoid esophagus exceeding 6 cm in diameter who have failed prior interventions, esophagectomy should be considered.

EGJOO (EGJ Outflow Obstruction)

EGJ outflow obstruction is defined by an elevated median IRP in the setting of preserved peristalsis. This diagnosis requires careful confirmation with provocative testing, including multiple rapid swallows, rapid drink challenge, and solid swallows. Artifact from a tight hiatal hernia, obesity, and opioid use are extremely common causes of a falsely elevated IRP, making clinical correlation absolutely essential before assigning this diagnosis.

When symptomatic EGJOO is confirmed and the functional lumen imaging probe (FLIP) demonstrates a reduced distensibility index below 2.0 mm squared per mmHg, treatment may be considered following the same algorithmic approach used for achalasia.

Other Major Motility Disorders

Distal Esophageal Spasm (DES)

Distal esophageal spasm is diagnosed when premature contractions with a distal latency below 4.5 seconds are present in more than 20% of wet swallows, with a crucially normal median IRP. The normal IRP is the distinguishing feature that separates DES from type III achalasia. Treatment options include smooth muscle relaxants, tricyclic antidepressants, and phosphodiesterase-5 inhibitors such as sildenafil at 50 mg. For patients refractory to medical therapy, POEM may be considered.

Hypercontractile Esophagus (Jackhammer)

Hypercontractile esophagus, or jackhammer esophagus, is defined by a DCI exceeding 8000 mmHg-s-cm in more than 20% of swallows. It is important to note that a single swallow with a DCI above 8000 constitutes a hypercontractile swallow but is insufficient for a diagnosis of hypercontractile esophagus. Before establishing this diagnosis, clinicians must exclude opioid use, eosinophilic esophagitis, and mechanical obstruction. Treatment mirrors that of DES, with smooth muscle relaxants and TCAs as first-line options and POEM reserved for refractory cases.

Absent Contractility

Absent contractility is characterized by 100% failed peristalsis with a normal IRP, distinguishing it from achalasia. This disorder is strongly associated with systemic sclerosis (scleroderma) and severe gastroesophageal reflux disease. The diagnosis carries important pre-operative implications: a full 360-degree fundoplication (Nissen) is contraindicated in the setting of absent contractility, although a partial fundoplication may be considered cautiously.

Ineffective Esophageal Motility (IEM)

Ineffective esophageal motility is diagnosed when more than 70% of swallows are ineffective, defined as failed or weak with a DCI below 450 mmHg-s-cm. The clinical significance of IEM remains debated, though it may contribute to GERD and dysphagia. In patients undergoing anti-reflux surgery, a full fundoplication should be avoided in favor of a partial wrap to reduce the risk of post-operative dysphagia.

Functional Lumen Imaging Probe (FLIP)

The functional lumen imaging probe is a balloon-based impedance planimetry device that simultaneously measures cross-sectional area and pressure at the EGJ, providing a complementary assessment of EGJ mechanics during sedated endoscopy. The distensibility index (DI), calculated as cross-sectional area divided by pressure at a fill volume of 40 to 60 mL, provides a quantitative measure of EGJ opening.

A DI below 2.0 mm squared per mmHg suggests impaired EGJ opening consistent with the achalasia spectrum. Values between 2.0 and 2.9 are considered borderline, while a DI above 3.0 is normal.

FLIP is increasingly utilized intraoperatively to assess the adequacy of myotomy during LHM or POEM, with a target DI above 4.5 to 5.0 mm squared per mmHg indicating successful disruption of the hypertonic sphincter.

<image>A cross-sectional diagram of the FLIP (Functional Lumen Imaging Probe) catheter positioned at the gastroesophageal junction. Show the balloon inflated across the GEJ with impedance electrode pairs labeled along the catheter. Include a schematic of the FLIP topography display (similar to HRM Clouse plot but showing diameter over time) with normal repetitive antegrade contractions in one panel and absent contractions (achalasia pattern) in another panel. Color code the topography: blue for narrow diameter, green-yellow for moderate, red for wide opening. Label the distensibility index calculation formula (DI = CSA / pressure) and show representative values for normal (DI >3.0) vs. achalasia (DI <2.0). Include a small inset showing the balloon's position relative to the diaphragmatic hiatus and LES.</image>

Key Clinical Pearls

• Always exclude pseudoachalasia in patients >55 years with short symptom duration — EUS and CT are essential
• Type II achalasia has the best treatment outcomes regardless of modality
• POEM is preferred for type III achalasia due to ability to perform extended myotomy
• Timed barium swallow is the best objective measure for post-treatment follow-up
• FLIP distensibility index <2.0 mm²/mmHg during sedated EGD should prompt manometric evaluation
• Post-POEM GERD is common (40-60%); all patients need PPI and surveillance for Barrett esophagus
• Opioids are the most common cause of artifactually elevated IRP and EGJOO — always review medication list
• Chicago Classification v4.0 requires supine AND upright swallows for definitive diagnosis of major disorders

References

1. Yadlapati R, et al. Esophageal motility disorders on high-resolution manometry: Chicago Classification version 4.0. Neurogastroenterol Motil. 2021;33(1):e14058.
2. Vaezi MF, Pandolfino JE, Yadlapati R, et al. ACG Clinical Guidelines: Diagnosis and Management of Achalasia. Am J Gastroenterol. 2020;115(9):1393-1411.
3. Werner YB, et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381(23):2219-2229.
4. Moonen A, et al. Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016;65(5):732-739.
5. Khashab MA, et al. ASGE guideline on the management of achalasia. Gastrointest Endosc. 2020;91(2):213-227.

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