Gaëlle Leroux

Common and unique components of inhibition and working memory : An fMRI, within-subjects investigation

Behavioural findings indicate that the core executive functions of inhibition and working memory are closely linked, and neuroimaging studies indicate overlap between their neural correlates. There has not, however, been a comprehensive study, including several inhibition tasks and several working memory tasks, performed by the same subjects. In the present study, 11 healthy adult subjects completed separate blocks of 3 inhibition tasks (a stop task, a go/no-go task and a flanker task), and 2 working memory tasks (one spatial and one verbal). Activation common to all 5 tasks was identified in the right inferior frontal gyrus, and, at a lower threshold, also the right middle frontal gyrus and right parietal regions (BA 40 and BA 7). Left inferior frontal regions of interest (ROIs) showed a significant conjunction between all tasks except the flanker task. The present study could not pinpoint the specific function of each common region, but the parietal region identified here has previously been consistently related to working memory storage and the right inferior frontal gyrus has been associated with inhibition in both lesion and imaging studies. These results support the notion that inhibitory and working memory tasks involve common neural components, which may provide a neural basis for the interrelationship between the two systems.

Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus.

Background: Poor adherence to treatment is difficult to diagnose accurately. Hydroxychloroquine (HCQ) has a long elimination half-life and its concentration in whole blood can be measured easily. Objective: To evaluate the utility of a very low blood HCQ concentration as a marker of poor compliance in patients with systemic lupus erythematosus (SLE). Methods: HCQ concentrations were determined on a blinded basis in 203 unselected patients with SLE. At the end of the study, the patients were informed of the results and retrospectively interviewed about their adherence to treatment. Results: 14 (7%) patients said that they had stopped taking HCQ (n = 8) or had taken it no more than once or twice a week (n = 6). Their mean (SD) HCQ concentration was 26 (46) ng/ml. range (0–129 ng/ml) By contrast, the other patients had a mean HCQ concentration of 1079 ng/ml range (205–2629 ng/ml). The principal barriers to adherence were related to HCQ treatment characteristics. Adherence subsequently improved in 10 of the 12 patients whose blood HCQ concentrations were remeasured. Conclusions: Very low whole-blood HCQ concentrations are an objective marker of prolonged poor compliance in patients with SLE. Regular drug assays might help doctors in detect non-compliance and serve as a basis for counselling and supporting these patients.

Posterior reversible encephalopathy syndrome during systemic lupus erythematosus: four new cases and review of the literature:

Posterior reversible encephalopathy syndrome (PRES) associates various neurological manifestations (headaches, seizures, altered mental status, cortical blindness, focal neurological deficits, vomiting) and transient changes on neuroimaging consistent with cerebral edema. Posterior reversible encephalopathy syndrome mainly occurs in the setting of hypertension, eclampsia, renal failure and/or use of immunosuppressive drugs. We report four cases of PRES complicating systemic lupus erythematosus (SLE). In all our cases, renal involvement and hypertension were present. Neurological symptoms were typical. Magnetic resonance imaging showed posterior cerebral edema and in one case hemorrhagic complication. With symptomatic treatment and immunosuppressor withdrawal when they were previously used, symptoms fully resolved within 15 days in all cases, but one who had only partial regression related to cerebral hemorrhage. Including our cases, we reviewed a total of 46 patients with SLE and PRES. Their clinical and radiological presentation was not specific. The peculiar role of SLE itself in the occurrence of PRES was not clear, since hypertension (95%), renal involvement (91%), recent onset of immunosuppressive drugs (54%) and/or recent treatment with high intravenous dose of steroids (43%) were often present. The hypertension and other worsening factors should be treated. Finally, the evolution of this clinical and radiological spectacular syndrome is generally rapidly favorable. Lupus (2008) 17, 139—147.

Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).

Introduction Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. Patients and methods [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. Results Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). Conclusions Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up. ClinicalTrials.gov NCT00413361

Functional Magnetic Resonance Imaging Study of Piaget's Conservation-of-Number Task in Preschool and School-Age Children: A Neo-Piagetian Approach.

Jean Piagets theory is a central reference point in the study of logico-mathematical development in children. One of the most famous Piagetian tasks is number conservation. Failures and successes in this task reveal two fundamental stages in childrens thinking and judgment, shifting at approximately 7 years of age from visuospatial intuition to number conservation. In the current study, preschool children (nonconservers, 5-6 years of age) and school-age children (conservers, 9-10 years of age) were presented with Piagets conservation-of-number task and monitored by functional magnetic resonance imaging (fMRI). The cognitive change allowing children to access conservation was shown to be related to the neural contribution of a bilateral parietofrontal network involved in numerical and executive functions. These fMRI results highlight how the behavioral and cognitive stages Piaget formulated during the 20th century manifest in the brain with age.

A New Presentation of Neonatal Lupus: 5 Cases of Isolated Mild Endocardial Fibroelastosis Associated with Maternal Anti-SSA/Ro and Anti-SSB/La Antibodies

Objective. Maternal anti-SSA/Ro or anti-SSB/La antibodies are associated with neonatal lupus erythematosus syndrome (NLES), especially congenital heart block (CHB), which may be associated with severe endocardial fibroelastosis (EFE) and dilated cardiomyopathy (DCM). A few reports have described severe EFE without CHB associated with anti-SSA/Ro antibodies, with a poor prognosis. EFE has also been observed in biopsies of DCM that had been considered idiopathic. These points, considered in association with 5 unusual cases of mild EFE, led us to consider the relationship between underrecognized cases of isolated autoantibody-associated EFE and DCM that had been considered idiopathic. Methods. We analyzed 5 cases of EFE diagnosed in utero (n = 4) or after birth (n = 1). In 3 cases, maternal antibody status was discovered because of the EFE diagnosis. Results. Endomyocardial hyperechogenicity predominated in the left atrium (n = 3) and mitral annulus (n = 3). No left-heart dysfunction was observed. Two mothers were treated with betamethasone. One mother chose to have a therapeutic abortion, and EFE was confirmed at autopsy. Electrocardiograms at birth (n = 4) did not show CHB. Other manifestations of NLES were present in all cases. One child had right ventricular hypoplasia and underwent a partial cavopulmonary anastomosis. At last followup (4–7 yrs), the other 3 children had normal heart function, and echocardiography showed a normal heart (n = 2) or mild persistent EFE (n = 1). Conclusion. Middle-term prognosis of isolated autoantibody-associated EFE may be better than previously reported, although the longterm prognosis remains unknown. We hypothesize that a fetal insult can lead to DCM.

The Shift from Local to Global Visual Processing in 6-Year-Old Children Is Associated with Grey Matter Loss

Background A real-world visual scene consists of local elements (e.g. trees) that are arranged coherently into a global configuration (e.g. a forest). Children show psychological evolution from a preference for local visual information to an adult-like preference for global visual information, with the transition in visual preference occurring around 6 years of age. The brain regions involved in this shift in visual preference have not been described. Methods and Results We used voxel-based morphometry (VBM) to study children during this developmental window to investigate changes in gray matter that underlie the shift from a bias for local to global visual information. Six-year-old children were assigned to groups according to their judgment on a global/local task. The first group included children who still presented with local visual processing biases, and the second group included children who showed global visual processing biases. VBM results indicated that compared to children with local visual processing biases, children with global visual processing biases had a loss of gray matter in the right occipital and parietal visuospatial areas. Conclusions These anatomical findings are in agreement with previous findings in children with neurodevelopmental disorders and represent the first structural identification of brain regions that allow healthy children to develop a global perception of the visual world.

BIL&GIN: A neuroimaging, cognitive, behavioral, and genetic database for the study of human brain lateralization.

We report on a database, named BIL&GIN, designed for investigating the cognitive, behavioral, genetic, and brain morphological/functional correlates of hemispheric specialization. The database contains records from a sample of 453 adult participants enriched in left-handers (45%, N=205) as compared to the general population. For each subject, socio-demographic data, hand and eye laterality, family handedness, and cognitive abilities in the language, motor, visuo-spatial, and numerical domains have been recorded. T1-MRI and DTI data were also acquired, as well as resting-state functional MRI. Task-evoked functional MRI was performed in a sub-sample of 303 subjects (157 left-handers) using a customized functional battery of 16 cognitive tasks exploring the same three cognitive domains. Performances at the tasks executed in the magnet as well as post-acquisition debriefing were recorded. A saliva sample was obtained from the subjects of this sub-sample from which DNA was extracted. The BIL&GIN contains results of imaging data processing for each subject, namely maps of tissue (GM, WM, CSF) probability, cortical thickness, cortical surface, and diffusion parameters as well as regional values of these phenotypes for regions of both AAL and FreeSurfer parcellations. For the subjects who underwent FMRI, individual SPM contrast maps for each of the 8 runs were also calculated and included in the database, as well as corresponding BOLD variations in ROIs of the AAL and AICHA atlases, and Wilkes hemispheric functional lateralization index. The BIL&GIN data sharing is based on a collaborative model.

Long-term outcome of 32 patients with chorea and systemic lupus erythematosus or antiphospholipid antibodies.

The aim of this work was to describe chorea during systemic lupus erythematosus or antiphospholipid antibodies and its long‐term outcome.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.