Botulinum Toxin Reduces Dysphagia in Patients With Nonachalasia Primary Esophageal Motility Disorders

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Endoscopic injection of botulinum toxin (BTX) has shown benefits for patients with diffuse esophageal spasm (DES) and nutcracker esophagus (NE) in small uncontrolled trials. We investigated the effect of BTX on symptoms of patients with DES or NE and assessed manometry findings in a prospective, double-blind, randomized, controlled study.


We assessed 22 patients with dysphagia-predominant, manometry-confirmed DES or NE (6 men; age, 63 ± 2 y) at a tertiary care medical center. Patients were given injections of BTX (8 × 12.5 U) or saline (8 × 0.5 mL) in 4 quadrants, at 2 and 7 cm above the esophagogastric junction. After 1 month, patients crossed over between groups and received endoscopic injections of BTX or saline. When the study began and 4 weeks after each injection, the patients were assessed by esophageal manometry and completed a symptom questionnaire (to determine solid and liquid dysphagia, chest pain, and regurgitation and heartburn; all scored 0–4). Responders were defined based on modified Vantrappen criteria for achalasia.


After BTX injections, patients had significant decreases in total symptom scores (sum of solid and liquid dysphagia and chest pain; from 7.6 ± 0.7 to 4.8 ± 0.8;P= .01); this decrease was not observed in patients who received saline injections. Moreover, BTX injection stabilized unintentional weight loss (weight gain of 0.3 ± 0.3 after BTX injection vs further weight loss of 1.6 ± 0.5 kg after saline injection;P= .01). Fifty percent of patients had a response 1 month after BTX injection, compared with 10% after saline injection (P= .04); 30% still had a response 1 year after BTX injection. BTX injection also caused a significant decrease in the mean esophagogastric junction pressure, compared with baseline (15.8 ± 1.7 vs 24.0 ± 2.8 mm Hg;P= .02).


In a prospective controlled study of patients with DES and NE, injections of BTX reduced symptoms and stabilized unintentional weight loss. Trial registry:, ML2669, ML6294.

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