Transient cortico-cortical disconnection during psychogenic nonepileptic seizures (PNES)

Psychogenic nonepileptic seizures (PNES) are paroxysmal clinical events that are often misdiagnosed as epileptic seizures, but which are not associated with electrographic discharge. Brain connectivity changes occurring during PNES are not known. We studied functional connectivity (Fc) in two patients with drug-resistant epilepsy, explored by stereotactic electroencephalography (EEG), in whom we recorded both epileptic seizures (ES) and PNES. Functional connectivity using pair-wise nonlinear correlation was computed between signals from seven brain areas: amygdala, hippocampus, lateral temporal cortex, anterior insula, orbitofrontal cortex, prefrontal cortex, and lateral parietal cortex. We assessed changes in global Fc during PNES in comparison with a background period. During PNES, a global decrease of Fc occurred between the different brain regions studied, compared with the interictal period. In both patients, decreased Fc was prominent in connections involving the anterior insula and parietal cortex. In conclusion, some PNES are associated with ictal functional disconnection between brain areas, particularly involving the parietal cortices and the anterior insula.     

Neural connectivity between the hypothalamic supramammillary nucleus and appetite‐ and motivation‐related regions of the rat brain

The supramammillary nucleus (SuM) has an emerging role in appetite control. We have shown that the rat SuM is activated during hunger or food anticipation, or by ghrelin administration. In the present study, we characterised the connectivity between the SuM and key appetite‐ and motivation‐related nuclei in the rat. In adult wild‐type rats, or rats expressing Cre recombinase under the control of the tyrosine hydroxylase (TH) promoter (TH‐Cre rats), we used c‐Fos immunohistochemistry to visualise and correlate the activation of medial SuM (SuMM) with activation in the lateral hypothalamic area (LH), the dorsomedial hypothalamus (DMH) or the ventral tegmental area (VTA) after voluntary consumption of a high‐sugar, high‐fat food. To determine neuroanatomical connectivity, we used retrograde and anterograde tracing methods to specifically investigate the neuronal inputs and outputs of the SuMM. After consumption of the food there were positive correlations between c‐Fos expression in the SuMM and the LH, DMH and VTA (P = 0.0001, 0.01 and 0.004). Using Fluoro‐Ruby as a retrograde tracer, we demonstrate the existence of inputs from the LH, DMH, VTA and ventromedial hypothalamus (VMH) to the SuMM. The SuMM showed reciprocal inputs to the LH and DMH, and we identified a TH‐positive output from SuMM to DMH. We co‐labelled retrogradely‐labelled sections for TH in the VMH, or for TH, orexin and melanin‐concentrating hormone in the LH and DMH. However, we did not observe any colocalisation of immunoreactivity with any retrogradely‐labelled cells. Viral mapping in TH‐Cre rats confirms the existence of a reciprocal SuMM‐DMH connection and shows that TH‐positive cells project from the SuMM and VTA to the lateral septal area and cingulate cortex, respectively. These data provide evidence for the connectivity of the SuMM to brain regions involved in appetite control, and form the foundation for functional and behavioural studies aiming to further characterise the brain circuitry controlling eating behaviours.     

Leptospirosis in Reunion Island (Indian Ocean): analysis of factors associated with severity in 147 confirmed cases

Objective Analysis of risk factors associated with severity in patients with confirmed leptospirosis. Design and setting Retrospective study in 147 leptospirosis-confirmed patients at two tertiary nonteaching hospital in Reunion Island. Patients 138 men and 9 women, aged 36 ± 14 years, 80 in the ICU and 67 in medical wards. Measurements and results We collected demographic, clinical, biological, and radiographic data and performed univariate and multivariate analysis to examine risk factors associated with admission in ICU and mortality. Pulmonary forms were more frequent (85%) than in previous reports, with 85 cases (65.3%) on abnormal chest radiography. Among the 38 patients who underwent bronchoalveolar lavage at admission 31 (81.5%) had alveolar hemorrhage. Independent factors related to ICU admission were: age over 46 years (OR 3.02), creatinine higher than 200 μmol/l (6.69), shock (13.87), and acute respiratory failure (20.69). Mortality was 12.9%. The only factor independently related to mortality was need for mechanical ventilation (OR 20.94). Icterohemorrhagiae serogroup was found in 62 cases (42.8%) but was not related to death. Conclusions Pulmonary involvement is a major feature in leptospirosis disease but is not associated with poor outcome. Identification of clinical and laboratory findings on admission may help to better characterize severe cases. Mailing address: Arnaud Bourdin is currently at the Service de Pneumologie, CHU Montpellier, France.     

A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy

BACKGROUND: Only 2 large (more than 100 patients) prospective trials comparing pancreatogastrostomy (PG) with pancreatojejunostomy (PJ) after pancreatoduodenectomy (PD) have been reported until now. One nonrandomized study showed that there were less pancreatic and digestive tract fistula with PG, whereas the other, a randomized trial from a single high-volume center, found no significant differences between the two techniques. METHODS: Single blind, controlled randomized, multicenter trial. The main endpoint was intra-abdominal complications (IACs). RESULTS: Of 149 randomized patients, 81 underwent PG and 68 PJ. No significant difference was found between the two groups concerning pre- or intraoperative patient characteristics. The rate of patients with one or more IACs was 34% in each group. Twenty-seven patients sustained a pancreatoenteric fistula (18%), 13 in PG (16%; 95% confidence interval [CI] 8-24%) and 14 in PJ (20%; 95% CI 10.5-29.5%). No statistically significant difference was found between the 2 groups concerning the mortality rate (11% overall), the rate of reoperations and/or postoperative interventional radiology drainages (23%), or the length of hospital stay (median 20.5 days). Univariate analysis found the following risk factors: (1) age > or =70 years old, (2) extrapancreatic disease, (3) normal consistency of pancreas, (4) diameter of main pancreatic duct <3 mm, (5) duration of operation >6 hours, and (6) a center effect. Significantly more IAC, pancreatoenteric fistula, and deaths occurred in one center (that included the most patients) (P = .05), but there were significantly more high-risk patients in this center (normal pancreas consistency, extrapancreatic pathology, small pancreatic duct, higher transfusion requirements, and duration of operation >6 hours) compared with the other centers. In multivariate analysis, the center effect disappeared. Independent risk factors included duration of operation >6 hours for IAC and for pancreatoenteric fistula (P = .01), extrapancreatic disease for pancreatoenteric fistulas (P < .04), and age > or =70 years for mortality (P < .02). CONCLUSIONS: The type of pancreatoenteric anastomosis (PJ or PG) after PD does not significantly influence the rate of patients with one or more IAC and/or pancreatic fistula or the severity of complications.     

Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study

Aims/hypothesis

The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk.

Methods

A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models.

Results

During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m² (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p _trend?<?0.0001 and p _trend?=?0.03, respectively). The NEAP score provided similar findings.

Conclusions/interpretation

We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.     

Endoscopic ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts

BACKGROUND: Surgery is the traditional treatment for symptomatic pancreatic pseudocysts, but the morbidity is still too high. Minimally invasive endoscopic approaches have been encouraged. AIMS: To evaluate the efficacy of endoscopic ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts. METHODS: From January, 2003 to August, 2006, 31 consecutive symptomatic patients submitted to 37 procedures at the same endoscopic unit were retrospectively analysed. Chronic and acute pancreatitis were found in, respectively, 17 (54.8%) and 10 (32.3%) cases. Bulging was present in 14 (37.8%) cases. Cystogastrostomy or cystoduodenostomy were created with an interventional linear echoendoscope under endosonographic and fluoroscopic control. By protocol, only a single plastic stent, without nasocystic drain, was used. Straight or double pigtail stents were used in, respectively, 22 (59.5%) and 15 (40.5%) procedures. RESULTS: Endoscopic ultrasound-guided transmural drainage was successful in 29 (93.5%) patients. Two cases needed surgery, both due to procedure-related complications. There was no mortality related to the procedure. Twenty-four patients were followed-up longer than 4 weeks. During a mean follow-up of 12.6 months, there were six (25%) symptomatic recurrences due to stent clogging or migration, with two secondary infections. Median time for developing complications and recurrence of the collections was 3 weeks. These cases were successfully managed with new stents. Complications were more frequent in patients treated with straight stents and in those with a recent episode of acute pancreatitis. CONCLUSIONS: Endoscopic transmural drainage provides an effective approach to the management of pancreatic pseudocysts.     

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.