Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in
Patients With Chronic Unexplained Nausea and Vomiting.
Authors Angeli TR, Cheng LK, Du P, Wang TH, Bernard CE, Vannucchi MG,
Faussone-Pellegrini MS, Lahr C, Vather R, Windsor JA, Farrugia G, Abell TL,
O'Grady G
Submitted By Thomas Abell on 11/3/2015
Status Published
Journal Gastroenterology
Year 2015
Date Published 7/1/2015
Volume : Pages 149 : 56 - 66.e5
PubMed Reference 25863217
Abstract Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of
unknown cause. Symptoms of CUNV substantially overlap with those of
gastroparesis, therefore the diseases may share pathophysiologic features. We
investigated this hypothesis by quantifying densities of interstitial cells of
Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs
controls., Clinical data and gastric biopsy specimens were collected from 9
consecutive patients with at least 6 months of continuous symptoms of CUNV but
normal gastric emptying who were treated at the University of Mississippi
Medical Center, and from 9 controls (individuals free of gastrointestinal
disease or diabetes). ICCs were counted and ultrastructural analyses were
performed on tissue samples. Slow-wave propagation profiles were defined by
high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results from
patients with CUNV were compared with those of controls as well as patients with
gastroparesis who were studied previously by identical methods., Patients with
CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively;
P < .05), with mild ultrastructural abnormalities in the remaining ICCs.
Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of
9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic
pacemakers, unstable focal activities) and conduction (retrograde propagation,
wavefront collisions, conduction blocks, and re-entry), operating across
bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric frequencies;
dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s
circumferential; P < .01). ICCs were less depleted in patients with CUNV than in
those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05),
but slow-wave dysrhythmias were similar between groups., This study defined
cellular and bioelectrical abnormalities in patients with CUNV, including the
identification of slow-wave re-entry. Pathophysiologic features of CUNV were
observed to be similar to those of gastroparesis, indicating that they could be
spectra of the same disorder. These findings offer new insights into the
pathogenesis of CUNV and may help to inform future treatments.

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