Miguel Angelo N. Souza

Visualization of vascular compression of the trigeminal nerve with high-resolution 3T MRI: a prospective study comparing preoperative imaging analysis to surgical findings in 40 consecutive patients who underwent microvascular decompression for trigeminal neuralgia.

BACKGROUND:High-resolution three-dimensional (3D) magnetic resonance imaging (MRI) has demonstrated its ability to predict fine trigeminal neurovascular anatomy. OBJECTIVE:To address the predictive value of 3-Tesla (3T) MRI in detecting and assessing features of neurovascular compression (NVC), particularly regarding the degree of compression exerted on the root, in patients who underwent microvascular decompression (MVD) for classic primary trigeminal neuralgia. METHODS:This prospective study includes 40 consecutive patients who underwent MVD for classic primary trigeminal neuralgia. All patients underwent a preoperative 3T MRI with 3D T2-weighted driven equilibrium (DRIVE), 3D time-of-flight (TOF) magnetic resonance angiography (MRA), and 3D T1-weighted gadolinium-enhanced sequences in combination. Evaluations were performed by 2 independent observers and compared with the operative findings. RESULTS:For prediction of NVC, image analysis corresponded with surgical findings in 39 cases. Of the 3 patients in whom image analysis did not show NVC, 2 did not have NVC at the time of intraoperative observation. MRI sensitivity was 97.4% (37/38), and specificity was 100% (2/2). The kappa coefficients (κ) for predicting the offending vessel, its location, and the site of compression were 0.882, 0.813, and 0.942, respectively. Image analysis correctly defined the severity of the compression in 31 of the 37 cases. The κ coefficients predicting the degree of compression were 0.813, 0.833, and 0.852, respectively, for Grades 1 (simple contact), 2 (distortion), and 3 (marked indentation). CONCLUSION:3T MRI using 3D T2-weighted DRIVE in combination with 3D TOF-MRA and 3D T1-weighted gadolinium-enhanced sequences proved to be reliable in detecting NVC and in predicting the degree of root compression, the outcome being correlated with the latter.

Structural abnormalities of the trigeminal root revealed by diffusion tensor imaging in patients with trigeminal neuralgia caused by neurovascular compression: A prospective, double-blind, controlled study

Summary A diffusion tensor imaging technique demonstrated alteration in the fraction of anisotropy and apparent diffusion coefficient values of the affected trigeminal nerve, suggesting structural or functional changes in patients with neurovascular compression‐induced trigeminal neuralgia. Abstract Because diffusion tensor imaging (DTI) is able to assess tissue integrity, we used diffusion to detect abnormalities in trigeminal nerves (TGN) in patients with trigeminal neuralgia (TN) caused by neurovascular compression (NVC). We also studied anatomical TGN parameters (cross‐sectional area [CSA] and volume [V]). Using DTI sequencing in a 3‐T magnetic resonance imaging (MRI) scanner, we measured the fraction of anisotropy (FA) and the apparent diffusion coefficient (ADC) of TGN in 10 patients selected as candidates to have microvascular decompression (MVD) for TN, and 6 normal control subjects. We compared data between the affected nerves of TN (ipsilateral TN), unaffected nerves of TN (contralateral TN), and both nerves in normal subjects (controls), and correlated these data with CSA and V. The FA of the ipsilateral TN (0.37 ± 0.08) was significantly lower (P < .05) compared with the contralateral TN (0.48 ± 0.08) and control values (0.52 ± 0.04). The ADC of ipsilateral TN (5.6 ± 0.89 mm2/s) was significantly higher (P < .05) compared with the contralateral TN (4.26 ± 0.59 mm2/s) and control values (3.84 ± 0.43 mm2/s). Ipsilateral TN had less V and CSA compared with contralateral TN and control values (P < .05). The Spearman correlation coefficient showed a strong positive correlation between loss of FA and loss of V (r = 0.7576) and loss of CSA (r = 0.9273) of affected nerves. The Spearman correlation coefficient showed a strong negative correlation between increase in ADC and loss of V (r = −0.7173) and loss of CSA (r = −0.7416) in affected nerves. DTI revealed alteration in the FA and ADC values of the affected TGN. These alterations were correlated with atrophic changes in patients with TN caused by NVC.

Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes

OBJECT The aim of this study was to prospectively evaluate atrophic changes in trigeminal nerves (TGNs) using measurements of volume (V) and cross-sectional area (CSA) from high-resolution 3-T MR images obtained in patients with unilateral trigeminal neuralgia (TN), and to correlate these data with patient and neurovascular compression (NVC) characteristics and with clinical outcomes. METHODS Anatomical TGN parameters (V and CSA) were obtained in 50 patients (30 women and 20 men; mean age 56.42 years, range 22-79 years) with classic TN before treatment with microvascular decompression (MVD). Parameters were compared between the symptomatic (ipsilateralTN) and asymptomatic (contralateralTN) sides of the face. Twenty normal control subjects were also included. Two independent observers blinded to the side of pain separately analyzed the images. Measurements of V (from the pons to the entrance of the nerve into Meckels cave) and CSA (at 5 mm from the entry of the TGN into the pons) for each TGN were performed using imaging software and axial and coronal projections, respectively. These data were correlated with patient characteristics (age, duration of symptoms before MVD, side of pain, sex, and area of pain distribution), NVC characteristics (type of vessel involved in NVC, location of compression along the nerve, site of compression around the circumference of the root, and degree of compression), and clinical outcomes at the 2-year follow-up after surgery. Comparisons were made using Bonferronis test. Interobserver variability was assessed using the Pearson correlation coefficient. RESULTS The mean V of the TGN on the ipsilateralTN (60.35 ± 21.74 mm(3)) was significantly smaller (p < 0.05) than those for the contralateralTN and controls (78.62 ± 24.62 mm(3) and 89.09 ± 14.72 mm(3), respectively). The mean CSA of the TGN on the ipsilateralTN (4.17 ± 1.74 mm(2)) was significantly smaller than those for the contralateralTN and controls (5.41 ± 1.89 mm(2) and 5.64 ± 0.85 mm(2), respectively). The ipsilateralTN with NVC Grade III (marked indentation) had a significantly smaller mean V than the ipsilateralTN with NVC Grade I (mere contact), although it was not significantly smaller than that of the ipsilateralTN with NVC Grade II (displacement or distortion of root). The ipsilateralTN with NVC Grade III had a significantly smaller mean CSA than the ipsilateralTN with NVC Grades I and II (p < 0.05). The TGN on the ipsilateralTN in cured patients had a smaller mean CSA than that on the ipsilateralTN of patients with partial pain relief or treatment failure (p < 0.05). The same finding was almost found in relation to measurements of V, but the p value was slightly higher at 0.05. CONCLUSIONS Results showed that TGN atrophy in patients with TN can be demonstrated by high-resolution imaging. These data suggest that atrophic changes in TGNs, which significantly correlated with the severity of compression and clinical outcomes, may help to predict long-term prognosis after vascular decompression.

Sildenafil delays the intestinal transit of a liquid meal in awake rats

Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

Gastric Emptying and Gastrointestinal Transit of Liquid in Awake Rats Is Delayed After Acute Myocardial Infarction

The outcome of acute myocardial infarction (AMI) on gastrointestinal motor behavior was assessed in awake rats. Under anesthesia, they were submitted to thoracotomy followed or not by occlusion of the left coronary artery. Next day, they were gavage fed (1.5 ml) with phenol red in 5% glucose solution and sacrificed 10, 20, or 30 min later. Each subset consisted of 7 to 19 animals. Dye recovery in the stomach, proximal, mid, and distal small intestine was obtained by spectrophotometry. Infarcted left ventricle plus septum area was about 48.9 ± 2.8, 55.1 ± 6.7, and 54.1 ± 8.1% (respectively, for 10-, 20-, and 30-min subsets). AMI increased gastric dye retention by 25.5, 51.3, and 65.1% (respectively, for 10-, 20-, and 30-min subsets), while it decreased mid small intestine retention at 30 min (45.3%) as well as distal retention at 10 min (90.5%) and 20 min (90%). A positive correlation (rS =0.64) was found between infarcted area and gastric retention values at 10 min. AMI also increased (P < 0.05) central venous pressure values in all subsets (3.8 ± 0.2 vs. −2.1 ± 1.5, 1.4 ± 0.1 vs. 0.5 ± 0.2, and 1.6 ± 0.4 vs. −0.2 ± 0.3 cm H2O), while it decreased (P < 0.05) mean arterial pressure (95.0 ± 2.6 vs. 110.0 ± 3.9 and 106.0 ± 2.0 vs. 113.0 ± 3.0 mm Hg, respectively, at 10 and 30 min), and increased (P < 0.05) the 10-min heart rate values (429.6 ± 11.3 vs. 374.0 ± 19.8 bpm). Omeprazole pretreatment did not alter this phenomenon. In another group of rats, cardiac chemoreflex stimulation by i.v. phenylbiguanide increased gastric dye retention by 51.1%. In conclusion, AMI delays the gastric emptying and gastrointestinal transit of liquid in awake rats.

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD.NEW & NOTEWORTHY In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.

Tu1206 Dyspeptic Symptoms in Inflammatory Bowel Diseases (IBD) Are Associated With Prolonged Gastric Emptying and High Serum Leptin Levels

Background: Symptoms compatible with GI functional disorders are higher in patients with IBD compared with controls. We demonstrated that delayed gastric emptying was associated with dyspeptic symptoms in inactive Crohns disease. Serum ghrelin and leptin levels were elevated in IBD patients and it was described that these hormones couldmodify the gastrintestinal motility. High ghrelin or leptin serum concentrations are associated with symptoms in functional dyspepsia. The relationship between ghrelin and leptin with GI symptoms and gastric motility in IBD patients has not been studied. Aim: To investigate the relationship between dyspeptic symptoms, gastric emptying, serum levels of ghrelin and leptin in IBD. Methods: Twenty seven patients with IBD (14 with Crohns disease and 13 with ulcerative colitis) underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (PADYQ, The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms; fasting blood samples were also collected to measure active ghrelin or leptin by a RIA. Then, IBD patients were allocated in two groups according to their total PADYQ score: non-dyspeptic (score=0), dyspeptic (score > 0). Control group was composed by 26 sex-matched healthy volunteers. The study was approved by the local Ethical Committee (049.07.08). Results: IBD patients had a significantly (p<0.01) slower gastric emptying (t1⁄2= 243.9 ± 14.2 min) than the controls (t1⁄2= 174.1 ± 6.3 min). IBD patients with dyspepsia (t1⁄2=265.9 ± 21.7 min, N=14) had significantly (p<0.05) prolonged gastric emptying when compared to IBD patients without dyspeptic symptoms (t1⁄2= 220.2 ± 16.1 min, N=13). Leptin (25.9 ± 5.8 ng/ml), but not active ghrelin (28.5 ± 2.4 pg/ml), was significantly (p<0.05) higher in IBD patients with dyspepsia than in IBD patients without dyspepsia (leptin= 13.7 ± 3.4 ng/ml, ghrelin=33.2 ± 6.0 pg/ml). In IBD patients with dyspepsia, only vomiting had positive linear correlation with gastric emptying (t1⁄2) (p=0.03) and leptin levels (p=0.06). No difference between the subgroups of patients with respect to type of disease (Crohn or ulcerative colitis), gender or age was found. However, the group with dyspepsia had more patients with active diseases than the group without dyspepsia (p<0.01). Conclusion: In IBD patients, dyspeptic symptoms, particularly vomiting, were associated with prolonged gastric emptying, high leptin serum levels and the presence of disease activity. The clinical relevance of the present findings remains to be demonstrated. Financial support: Capes, CNPq.

Acute intracranial hypertension increases gastric tonus in anesthetized rats

We studied the acute effect of intracranial hypertension (ICH) on gastric tonus of anesthetized rats. Brain ventricles were cannulated bilaterally for intracerebro-ventricular pressure (ICP) monitoring and ICH induction. Next, a balloon catheter was inserted at the proximal stomach and coupled to a barostat for gastric volume (GV) monitoring by plethysmography. Arterial pressure (AP) and heart rate (HR) were monitored continuously during 80-min. After a 20-min basal period, they were submitted to control or ICH protocols. In controls, the ICP varied spontaneously up to the end. Other rats were subjected to ICP rising to 10, 20, 40 or 60 mmHg and kept at these levels for 30-min. Another group was subjected after basal period to stepwise ICH (ICP rising to 20, 40 and 60 mmHg at every 10-min interval). Next, the ICH rats were monitored for further 30-min. Other rats, previously submitted to a subdiaphragmatic vagotomy, splanchnicectomy plus ganglionectomy or their respective sham surgery, were also studied under ICH. Each subset consisted of 5-6 rats. Data were compared to respective basal values after ANOVA and Bonferronis test. In controls, the GV, AP, HR values remained within stable levels. Besides inducing bradycardia and arterial hypertension, ICH10 mmHg decreased GV by 14.8% at the 50-min interval. In ICH20, 40 and 60 mmHg subsets, GV decreased 14.0, 24.5 and 30.6% at the 40-min interval, respectively. In stepwise ICH rats, GV decreased 10.2% and 12.7%, respectively under ICP of 40 and 60 mmHg. The GV values remained significantly lower than basal levels during the last 30-min of monitoring. Thus, ICH decreases the GV in an ICP-dependent pattern besides inducing Cushings reflex.

T1341 Mild Hypovolemia Delays Liquid Gastric Emptying and Decreases Gastric Tonus in Humans

with age, gender and calendar period. Results: Among 1568 potential cases of gastroparesis, 83 met diagnostic criteria for definite, 126 probable, and 221 possible. The age-adjusted (to 2000 U.S.whites) incidence per 100,000 person-years of definite gastroparesis for the years 1996-2006 was 2.5 (95% CI, 1.2-3.8) for men, and 9.8 (95% CI, 7.5-12.1) for women. The age-adjusted prevalence of definite gastroparesis per 100,000 person on January 1, 2007 was 9.6 (95% CI, 1.8-17.4) for men and 37.8 (95% CI, 23.2-52.4) for women. Poisson regression indicated significantly increasing rates with age and for females (both p<0.001) but no effect of calendar period. 18 (22%) with definite gastroparesis had diabetes mellitus, 36 (43%) were idiopathic and 29 (35%) other diseases. Overall survival was significantly lower than the age and gender specific expected survival computed from the Minnesota white population (p<0.05). Conclusions: Gastroparesis is an uncommon condition in the community, but overall survival is significantly decreased. Overall Incidence, Prevalence and Survival of Gastroparesis Among Olmsted County, Minnesota, 1996-2006