Adeyemi Lawal

Rapid Gastric Emptying Is More Common than Gastroparesis in Patients With Autonomic Dysfunction

OBJECTIVES:Autonomic dysfunction is associated with a wide variety of gastrointestinal symptoms. It is unclear how many patients with autonomic dysfunction have slow or rapid gastric emptying. The aim of this study was to determine the prevalence of rapid and delayed solid phase gastric emptying in patients with autonomic dysfunction referred for evaluation of gastrointestinal symptoms and the association of emptying rate with clinical symptoms.METHODS:Retrospective review of all patients with autonomic dysfunction who had a gastric emptying test from January, 1996 to March, 2005. Demographic data, clinical symptoms, composite autonomic scoring scale (CASS) score, and gastric emptying parameters were analyzed.RESULTS:Sixty-one subjects (women 49, age 42 [16–74] yr) with autonomic dysfunction were reviewed. Patients had mild-to-moderate (mean CASS score 3) autonomic dysfunction. Twenty-seven, 17, and 17 patients had rapid, normal, and delayed gastric emptying t1/2, respectively. In addition, 10 patients had initially rapid emptying in phase 1, with subsequent slowing in phase 2 to produce an overall normal or delayed t1/2. There was no difference in demographic data or CASS score among the three groups. More patients with initial or overall rapid emptying had diarrhea (70%) compared to patients with normal (33%) or delayed (33%) emptying (P = 0.018).CONCLUSIONS:Unexpectedly, more patients with autonomic dysfunction have rapid rather than delayed gastric emptying. The presence of diarrhea in patients with autonomic symptoms should prompt consideration for the presence of rapid gastric emptying. Conversely, the finding of rapid gastric emptying in patients with gastrointestinal symptoms should prompt consideration for the presence of underlying autonomic dysfunction.

Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus

The cingulate and insular cortices are parts of the limbic system that process and modulate gastrointestinal sensory signals. We hypothesized that sensitization of these two limbic area may operate in esophageal sensitization. Thus the objective of the study was to elucidate the neurocognitive processing in the cingulate and insular cortices to mechanical stimulation of the proximal esophagus following infusion of acid or phosphate buffer solution (PBS) into the esophagus. Twenty-six studies (14 to acid and 12 to PBS infusion) were performed in 20 healthy subjects (18-35 yr) using high-resolution (2.5 x 2.5 x 2.5 mm(3) voxel size) functional MRI (fMRI). Paradigm-driven, 2-min fMRI scans were performed during randomly timed 15-s intervals of proximal esophageal barostatically controlled distentions and rest, before and after 30-min of distal esophageal acid or PBS perfusion (0.1 N HCl or 0.1 M PBS at 1 ml/min). Following distal esophageal acid infusion, at subliminal and liminal levels of proximal esophageal distentions, the number of activated voxels in both cingulate and insular cortices showed a significant increase compared with before acid infusion (P < 0.05). No statistically significant change in cortical activity was noted following PBS infusion. We conclude that 1) acid stimulation of the esophagus results in sensitization of the cingulate and insular cortices to subliminal and liminal nonpainful mechanical stimulations, and 2) these findings can have ramifications with regard to the mechanisms of some esophageal symptoms attributed to reflux disease.

Effect of esophageal acid exposure on the cortical swallowing network in healthy human subjects

Recent studies have demonstrated common cortical activity regions associated with esophageal acidification and swallowing. The effect of sensory signals imparted on these regions by esophageal acidification on swallow-related brain activity has physiological and clinical ramifications. Our aim in this study was to determine the effect of prior, unperceived esophageal acid exposure on cortical activity associated with swallowing. Functional magnetic resonance imaging (fMRI) techniques monitored brain activity associated with volitional swallowing before and after subliminal esophageal acid stimulation. Studies were carried out in two phases. In phase I (15 healthy, right-handed subjects, age 21-49 yr, 7 female) using whole brain imaging, we documented the potentiating effects of esophageal acidification alone on swallow-related cortical activity. In phase II (10 healthy, right-handed subjects, age 20-54 yr, 5 female) using high-resolution fMRI, we measured swallow-induced regional brain activity within the cortical swallowing network before and after esophageal acidification. Unlike the phase I studies, we also tested the effect of saline perfusion alone on the cortical swallowing network in the phase II studies. Because of constraints imposed by high-resolution MRI for region-of-interest (ROI) analysis, we studied only the left hemisphere in this phase. None of the subjects developed heartburn during acid perfusion. In phase I, the number of swallow-induced activated voxels increased by 43% following esophageal acid stimulation (preacid, 44 +/- 3 voxels; postacid, 63 +/- 6 voxels; means +/- SE, P < 0.05) In phase II, contrary to saline perfusion, ROI analysis showed significantly increased regional swallow-related fMRI activity volumes as well as percent maximum signal change after esophageal acid perfusion in cingulate, prefrontal, insula, and sensory/motor regions (P < 0.05). The precuneus showed no significant change. We concluded that subliminal esophageal acid stimulation has a potentiating effect on the cortical swallowing network in healthy individuals.

907 GERD Alters the Functional Brain Connectivity Models Associated with Acid Stimulation

Previous fMRI studies have documented in healthy controls and GERD patients activation of sensory/motor (SM), prefrontal (PF), anterior (AC) and posterior (PC) cingulate and insula (I) brain regions associated with esophageal acid perfusion. GERD was found to significantly amplify the volume and intensity of fMRI signals compared to controls. (Kern M, Am J Physiol 2004; 286(1):G174-81) The effects of GERD on the connectivity of cortical networks have not been studied. Aim: To compare the functional connectivity models of brain regions showing fMRI activation during esophageal acid perfusion in GERD patients and healthy controls. Methods: Structural Equation Modeling (SEM) was used to generate partial regression coefficients representing the covariance among regional fMRI signals activated by esophageal acid perfusion. We studied 7 GERD patients (4 female, age range: 20-62 years) and 8 controls (4 female, age range: 22-40 years), during high spatial resolution fMRI scanning sequences. Brain images were acquired during alternating intervals of 0.1N HCl and saline perfusion of the distal esophagus. Grouped data was used in the SEM to yield maps showing significant (p<0.05, goodness-of-fit test) connectivity paths from a general network based on known anatomical connections among the brain regions. Results: There were substantial differences in the connectivity maps associated with esophageal acid perfusion in GERD compared to controls. As seen (Figure), arrows between regions show the direction of significant covariance. Partial regression coefficients for these paths represent a measure of the degree of correlation between the regions. For all network models, GERD connectivity was different than that of the controls. These differences were characterized by decreased connectivity between limbic and para-limbic structures like the AC and I as well as altered patterns of connectivity between PF, I and AC in GERD compared to controls. Conclusions: Models of brain connectivity associated with esophageal acid perfusion differ when comparing patients and controls suggesting alteration of the cerebral cortical networks associated with processing visceral sensory input in GERD.

Esophageal Adenocarcinoma: Pseudo-Nutcracker Esophagus

Pseudoachalasia due to adenocarcinoma is well known. We report a case of nutcracker esophagus in the setting of outflow obstruction from esophageal adenocarcinoma. Endoscopy is warranted to exclude similar lesions in patients with “pseudo-nutcracker esophagus”.

80 Upper Esophageal Sphincter and Gastroesophageal Junction Pressure Changes Act to Prevent Reflux During Obstructive Sleep Apnea in GERD Patients

Introduction: Gastroesophageal reflux (GER) is thought to be induced by deceasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. Aims: Determine UES and GEJ pressure change during OSA and characterize the GER and esophago-pharyngeal reflux (EPR) events during sleep. Methods: We studied 12 controls, 5 GERD without OSA and 6 GERD with OSA patients for 6-hours post-prandially during sleep. We concurrently recorded: a) UES, GEJ and esophageal body (ESO) pressures with a high-resolution manometric system. b) pharyngeal and esophageal reflux events by impedance and pH recordings. c) sleep stages and respiratory events using polysomnogram. End inspiration UES, GEJ and ESO pressures over intervals of OSA were averaged in GERD/OSA patients and compared to average values for randomly selected ten-second intervals during sleep in controls and GERD patients. Results: Total sleep time was 309±46, 317±39 and 306±58 minutes in controls, GERD and OSA patients, respectively. Our findings confirm previous reports of decreasing ESO pressures during OSA events, however, end-inspiratory UES and GEJ pressures at the end of OSA events were significantly higher than those at the beginning of OSA (p<0.01, Table 1). End-expiratory pressure in UES, GEJ and ESO at the beginning of OSA was not changed during OSA. Only two GER events during OSA were recorded in OSA patients. The incidence of GER and EPR events during sleep in GERD/OSA patients did not differ from those in controls and GERD patients (Table 2). Conclusion: Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent GERD patients with OSA from having an increase in reflux events.