Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting

Background & Aims 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. Methods 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 cm²). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. Results 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. Conclusions 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.