Specific Neuroanatomical Abnormalities Identified in Cyclical Vomiting Syndrome Based on Brain MRI Analysis

Abstract

Introduction: Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent abrupt bouts of nausea, vomiting, and abdominal pain separated by variable symptom-free periods. Major etiological factors include migraine, stress, and marijuana use (MU). A dysregulation of central neural pathways and neuro-endocrine mediators are hypothesized to play a role in pathophysiology. This study investigated whether there are neuroanatomical differences in CVS. Methods: 21 CVS patients and 15 healthy controls (HC) participated (Table 1). CVS patients were scanned during a symptomatic episode. 13 reported migraines, 12 high levels of stress, 10 chronic MU, and 6 all 3. High-resolution anatomical MPRAGE images were obtained in each participant. Images were preprocessed using standard pipelines in Freesurfer and tested for differences in cortical thickness and subcortical volume between CVS and HC. Surface-based results were thresholded and corrected for multiple comparisons using Monte Carlo simulation. Results: Surface-based cortical thickness analysis (Figure 1) revealed that CVS had significantly lower cortical thickness in bilateral precuneus (left: p =.001; right: p=.0002), left superior frontal gyrus (p=.008), and right precentral gyrus (p=.0084) than a HC. No cortical differences were found between MU and non-marijuana use (Non-MU) subgroup of CVS patients. Subcortical results (Figure 2) identified reduced cortical volumes in Non-MU in bilateral hippocampus (left: p=.002; right: p=.001) and amygdala (left: p=.023; right: p=.038). The MU had significantly greater cortical volumes in bilateral putamen (left: p=.05; right: p=.03) and pallidum (left: p=.004; right: p=.01) vs. non-MU but did not significantly differ from HC.437_A Figure 1. Subject demographics437_B Figure 2. Clusters showing lower cortical thickness in CVS patients relative to controls. Results are presented on the inflated cortical surface of the Freesurfer template. A) Medial view of left hemisphere showing precuneus cluster. B) Lateral view of left hemisphere showing superior frontal gyrus cluster. C) Medial view of right hemisphere showing precuneus cluster. D) Lateral view of right hemisphere showing precentral gyrus cluster.Conclusion: Based on brain MRI analysis we conclude that symptomatic CVS patients had cortical thinning relative to HC in precuneus and caudal regions of prefrontal/premotor cortex. Non-MU also had lower subcortical volume measures in the amygdala and hippocampus vs. HC. The precuneus is involved in visuo-spatial, vestibular processing and self-awareness, which suggests a potential sensory-integration or vestibular basis for CVS, while the amygdala and hippocampus are involved in processing pain, emotion, and stress. MU had greater basal ganglion cortical volumes consistent with increased dopaminergic stimulation. Our results provide evidence for a neuroanatomical basis of CVS with possible implications for future therapy.437_C Figure 3. Subcortical volumetric results. Error bars depict 95% Confidence Intervals (CI) within each Region of Interest (ROI).