Gastroenterology

Gastroenterology

Volume 149, Issue 1, July 2015, Pages 56-66.e5
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting

https://doi.org/10.1053/j.gastro.2015.04.003Get rights and content

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.

Section snippets

Materials and Methods

Ethical approval was granted by the New Zealand Regional Ethics Committee, and by the Institutional Review Boards at the University of Mississippi and Mayo Clinic. All patients provided informed consent.

Study Populations

The CUNV cohort consisted of 9 consecutive patients (4 diabetic), with a median 4-hour gastric retention of 4% (range, 2%–9%) and a median total symptom score of 16 (range, 9.5–20). The mean time from the gastric emptying test to surgery was 2.1 ± 2.3 months. The HR mapping controls also consisted of 9 patients of comparable age with the CUNV cohort (P = .14). Table 1 compares the CUNV and HR mapping control populations, with individual patient data provided in Supplementary Tables 1 and 2. The

Discussion

CUNV is accompanied by considerable morbidity, but has remained a poorly characterized disorder of unknown etiology. This study quantified ICC numbers and ultrastructural features, in combination with modern slow-wave mapping techniques,12 to investigate pathogenic mechanisms contributing to CUNV. It was found that CUNV patients had ICC depletion and abnormal slow-wave initiation and conduction, compared with controls. Further comparison with a historic cohort of gastroparetic patients9 showed

Acknowledgments

The authors thank the clinical research and operating room staff at the University of Mississippi Medical Center, and Mr Simon Bull and Ms Rachel Berry for their valued assistance.

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    Conflicts of interest This author discloses the following: Thomas Abell is a licensor, consultant, and investigator for Medtronic, Inc. The remaining authors disclose no conflicts.

    Funding Supported by the New Zealand Health Research Council, National Institutes of Health and the Gastroparesis Clinical Research Consortium (R01 DK64775, DK57061, DK73983, DK74008, and U01 DK074007), New Zealand Medical Technologies Centre of Research Excellence, a Young Investigator Clinical Research grant from the American Neurogastroenterology and Motility Society (G.O.G.), the Rutherford Foundation Trust (P.D.), and the Marsden Fund (P.D.).

    Author names in bold designate shared co-first authors.

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