Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of 
which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink 
challenge (RDC) are complementary tests used during high-resolution manometry 
(HRM) that evaluate inhibitory and excitatory neuromuscular function and latent 
obstruction, respectively. Our aim was to evaluate esophageal pathophysiology 
using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). 
Twenty-one healthy subjects (11 men; median age: 28 yr; range: 26-30 yr) were 
used as a control group. All patients underwent solid-state HRM with ten 5-ml 
single swallows (SS) and one to three 10-ml MRS; 34 patients also underwent RDC. 
Data are shown as median (interquartile range). Abnormal motor inhibition was 
noted during at least one MRS test in 48% of JE patients compared with 29% of 
controls ( P = 0.29). Mean distal contractile integral (DCI) after MRS was 
significantly lower than after SS [6,028 (3,678-9,267) mmHg·cm·s vs. 7,514 
(6,238-9,197) mmHg·cm·s, P = 0.02], as was highest DCI ( P < 0.0001). 
Consequently, 66% of JE patients had no contraction reserve. At least one 
variable of obstruction during RDC (performed in 34 patients) was outside the 
normal range in 25 (74%) of JE patients. Both highest DCI after SS and pressure 
gradient across the esophagogastric junction (EGJ) during RDC were higher in 
patients with dysphagia versus those without ( P = 0.04 and 0.01, respectively). 
Our data suggest altered neural control in JE patients with heterogeneity in 
inhibitory function. Furthermore, some patients had latent EGJ obstruction 
during RDC, which correlated with the presence of dysphagia. NEW & NOTEWORTHY 
Presence of abnormal inhibition was observed during multiple rapid swallows 
(MRS) in some but not all patients with jackhammer esophagus (JE). Unlike 
healthy subjects, JE patients were more strongly stimulated after single 
swallows than after MRS. An obstructive pattern was frequently observed during 
rapid drink challenge (RDC) and was related to presence of dysphagia. MRS and 
RDC during high-resolution manometry are useful to show individual 
pathophysiological patterns in JE and may guide optimal therapeutic strategies.