Stephen J. Antonik

Enhancing effects of flavored nutritive stimuli on cortical swallowing network activity

A better understanding of the central control of the physiology of deglutition is necessary for devising interventions aimed at correcting pathophysiological conditions of swallowing. Positive modulation of the cortical swallowing network can have clinical ramifications in dysphagia due to central nervous system deficits. Our aim was to determine the effect of nutritive sensory input on the cortical swallowing network. In 14 healthy right-handed volunteers, we utilized a paradigm-driven protocol to quantify the number of activated voxels and their signal intensity within the left hemispheric cortical swallowing network by high-resolution functional MRI (fMRI) during five different swallowing conditions. Swallowing conditions included a dry swallow (saliva) and natural water-, lemon-, popcorn-, and chocolate-flavored liquid swallows. Each flavored liquid was presented simultaneously by its image, scent, and taste in random order and tested over three runs. fMRIs were analyzed in a blinded fashion. Average fMRI blood oxygenation level-dependent signal intensity and number of activated voxels during swallowing concurrent with nutritive gustatory, olfactory, and visual stimulations were significantly increased compared with dry/natural water swallows throughout the cortical swallowing network (P < 0.001 and P < 0.05, respectively). Subregion analysis showed the increased activity for flavored liquids in prefrontal, cingulate gyrus, and sensory/motor cortex, but not in precuneus and insula. Concurrent gustatory, olfactory, and visual nutritive stimulation enhances the activity of the cortical swallowing network. This finding may have clinical implications in management of swallowing disorders due to cortical lesions.

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.

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.

M1158 Seasonal Variation in HRQOL and Disease Activity in Patients with Inflammatory Bowel Disease: A Tertiary Care Center Experience

G A A b st ra ct s maintenance organization (HMO) and describe its characteristics. Materials and methods: A retrospective, descriptive, cross sectional study was carried out. The electronic medical records from an HMO with a population mainly composed by urban middle class individuals were searched. Different keywords were used to select the group with greater chance of having IBD. The records were reviewed in order to confirm the diagnosis according to clinical findings and complementary studies and to describe the evolution and characteristics of the disease. Results: Among 147,109 individuals enrolled in the HMO, 687 were identified using the keywords. The diagnosis of IBD was established in 143 (M/F: 68/75), with an estimated prevalence of 97.2 per 100,000 (95% CI, 82.5-114.5). The prevalence of UC and CD was 76.1 (95% CI 63.2-91.6) and 15.0 (95% CI 9.8-22.7) per 100,000, respectively. Nine patients were diagnosed as indeterminate colitis with an estimated prevalence of 6,1 per 100,000 (95% CI 3.18-11.76). Among patients with UC (M/F: 52/60), the median age at the moment of diagnosis was 37.5 (r: 3-78) and 56.5% were between 10 to 40 years at onset. The most frequent clinical presentation was pancolitis (43%) and 31% of these patients underwent colectomy. The prevalence of primary schlerosing cholangitis was 6%. Among patients with CD (M/F: 13/9), the median age at the moment of diagnosis was 37.0 (r: 1181) and 53% were between 10 to 40 years at onset. The most frequently affected region was the terminal ileum. Nine patients underwent surgical procedures (41%). Patients with indeterminate colitis account for 6% of all IBD, with a median age at diagnosis of 63 (r: 28-83). The affected areas were rectum in 55% and left colon in 45%. Conclusion: The estimated prevalence of UC in an HMO population from Argentina is similar to previous reports from Europe and the U.S., although the estimated prevalence of CD is lower. Even though the study population is not a random sample and represents only a small percentage of Argentine inhabitants, the data we obtained may allow a better understanding of the epidemiology of IBD in Argentina.

M1156 Does Duration of Disease Impact Health Related Quality of Life (HRQOL) in Inflammatory Bowel Disease

G A A b st ra ct s maintenance organization (HMO) and describe its characteristics. Materials and methods: A retrospective, descriptive, cross sectional study was carried out. The electronic medical records from an HMO with a population mainly composed by urban middle class individuals were searched. Different keywords were used to select the group with greater chance of having IBD. The records were reviewed in order to confirm the diagnosis according to clinical findings and complementary studies and to describe the evolution and characteristics of the disease. Results: Among 147,109 individuals enrolled in the HMO, 687 were identified using the keywords. The diagnosis of IBD was established in 143 (M/F: 68/75), with an estimated prevalence of 97.2 per 100,000 (95% CI, 82.5-114.5). The prevalence of UC and CD was 76.1 (95% CI 63.2-91.6) and 15.0 (95% CI 9.8-22.7) per 100,000, respectively. Nine patients were diagnosed as indeterminate colitis with an estimated prevalence of 6,1 per 100,000 (95% CI 3.18-11.76). Among patients with UC (M/F: 52/60), the median age at the moment of diagnosis was 37.5 (r: 3-78) and 56.5% were between 10 to 40 years at onset. The most frequent clinical presentation was pancolitis (43%) and 31% of these patients underwent colectomy. The prevalence of primary schlerosing cholangitis was 6%. Among patients with CD (M/F: 13/9), the median age at the moment of diagnosis was 37.0 (r: 1181) and 53% were between 10 to 40 years at onset. The most frequently affected region was the terminal ileum. Nine patients underwent surgical procedures (41%). Patients with indeterminate colitis account for 6% of all IBD, with a median age at diagnosis of 63 (r: 28-83). The affected areas were rectum in 55% and left colon in 45%. Conclusion: The estimated prevalence of UC in an HMO population from Argentina is similar to previous reports from Europe and the U.S., although the estimated prevalence of CD is lower. Even though the study population is not a random sample and represents only a small percentage of Argentine inhabitants, the data we obtained may allow a better understanding of the epidemiology of IBD in Argentina.

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”.