Dépistage des troubles sémantiques dans les maladies d'Alzheimer et apparentées

La mémoire sémantique (MS) regroupe un ensemble des connaissances générales sur le monde. Elle repose sur des réseaux néocorticaux étendus qui convergent vers des « hubs » centraux situés au niveau des lobes temporaux. L'atteinte de la MS est au premier plan dans la démence sémantique (DS). Bien qu'elle soit fréquente dans la maladie d'Alzheimer (MA) et les maladies apparentées, elle n'est pas systématiquement recherchée car son évaluation exhaustive nécessite la réalisation, coûteuse en temps, de plusieurs tests. Objectif : L'objectif principal de cette étude était d'évaluer la performance d'un algorithme rapide de dépistage des troubles sémantiques, élaboré lors d'un précèdent travail dans une population de sujets atteints de troubles cognitifs légers (TCL) d'origine neurodégénérative. L'objectif secondaire était d'étudier son lien avec l'atrophie temporale. Méthode : Il s'agit d'une étude prospective, bi-centrique, menée dans les Centre de Mémoire de Ressource et de Recherche de Rouen et de Lille, de juin 2017 à avril 2019, incluant des sujets avec TCL d'origine neurodégénérative ayant un MMSE 20. Les performances de dépistage des troubles sémantiques de l'algorithme ont été comparées à un bilan orthophonique standard. L'algorithme reposait sur le test de dénomination orale des visages célèbres et la vérification écrite du GREMOTS, auxquels s'ajoutait la version image du « Pyramid and Palm Tree Test » (PPTT) si besoin. La valeur diagnostique des tests sémantiques d'intérêt a été évaluée individuellement à l'aide de la méthode bayésienne (PPTT versions mot et image, vérification orale et écrite et dénomination des visages célèbres du GREMOTS). Enfin, quand l'IRM cérébrale était disponible, l'atrophie temporale interne était évaluée à l'aide d'une échelle visuelle de gradation 0 à 3. Résultats : La population était composée de 23 patients, dont 13 MA, 4 DS, 2 dégénérescences lobaires fronto-temporales — variant comportemental, 2 aphasies progressives primaires logopéniques et 2 paralysies supranucléaires progressives. L'âge moyen était de 71 ans [56-85]. L'utilisation de l'algorithme permettait de classer correctement 15 sujets déficitaires avec une sensibilité de 93,8% [IC:42.1%-99.6%] et une spécificité de 85,7% [IC:69.8%-99.8%]. Un sujet était considéré déficitaire par notre algorithme mais pas par le bilan standard et un sujet n'était pas retenu déficitaire alors qu'il l'était par le bilan standard. La durée moyenne de passation des 2 premiers tests de notre algorithme était de 5,6 minutes [2,9-10,3]. Pour les 4 sujets nécessitant le troisième test pour conclure, la durée moyenne était de 13,6 minutes [8,3-17,8]. Les performances aux tests neuropsychologiques standards étaient similaires dans les deux groupes, avec ou sans déficit sémantique. L'effectif pour l'analyse IRM était insuffisant pour conclure sur le lien éventuel entre la sévérité de l'atrophie temporale interne et la présence d'un déficit sémantique. Conclusion : L'algorithme proposé permet de dépister de manière fiable l'atteinte de la MS chez des sujets avec TCL d'origine neurodégénérative L'utilisation des deux premiers tests (dénomination orale des visages célèbres et vérification écrite du GREMOTS) en moins de 6 minutes pourrait s'intégrer dans une consultation mémoire et permettre une orientation des patients vers une prise en charge orthophonique rapide et adaptée

Publisher Correction: Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienc

Carriage of third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales among children in sub-Saharan Africa: a systematic review and meta-analysisResearch in context

Summary: Background: The increasing resistance of Enterobacterales to third-generation cephalosporins and carbapenems in sub-Saharan Africa (SSA) is a major public health concern. We did a systematic review and meta-analysis of studies to estimate the carriage prevalence of Enterobacterales not susceptible to third-generation cephalosporins or carbapenems among paediatric populations in SSA. Methods: We performed a systematic literature review and meta-analysis of cross-sectional and cohort studies to estimate the prevalence of childhood (0–18 years old) carriage of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) or carbapenem-resistant Enterobacterales (CRE) in SSA. Medline, EMBASE and the Cochrane Library were searched for studies published from 1 January 2005 to 1 June 2022. Studies with <10 occurrences per bacteria, case reports, and meta-analyses were excluded. Quality and risk of bias were assessed using the Newcastle–Ottawa scale. Meta-analyses of prevalences and odds ratios were calculated using generalised linear mixed-effects models. Heterogeneity was assessed using I2 statistics. The protocol is available on PROSPERO (CRD42021260157). Findings: Of 1111 studies examined, 40 met our inclusion criteria, reporting on the carriage prevalence of Enterobacterales in 9408 children. The pooled carriage prevalence of ESCR-E was 32.2% (95% CI: 25.2%–40.2%). Between-study heterogeneity was high (I2 = 96%). The main sources of bias pertained to participant selection and the heterogeneity of the microbiological specimens. Carriage proportions were higher among sick children than healthy ones (35.7% vs 16.9%). The pooled proportion of nosocomial acquisition was 53.8% (95% CI: 32.1%–74.1%) among the 922 children without ESCR-E carriage at hospital admission. The pooled odds ratio of ESCR-E carriage after antibiotic treatment within the previous 3 months was 3.20 (95% CI: 2.10–4.88). The proportion of pooled carbapenem-resistant for Enterobacterales was 3.6% (95% CI: 0.7%–16.4%). Interpretation: This study suggests that ESCR-E carriage among children in SSA is frequent. Microbiology capacity and infection control must be scaled-up to reduce the spread of those multidrug-resistant microorganisms. Funding: There was no funding source for this study

Antimicrobial resistance in Enterobacterales infections among children in sub-Saharan Africa: a systematic review and meta-analysisResearch in context

Summary: Background: The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children. Methods: We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0–18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I2 statistic. The protocol was registered with PROSPERO (CRD42021260157). Findings: After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%–55%; I2: 85.7%, number of isolates (n): 1032) and 84.9% (72.8%–92.2%; I2: 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%–97.9%; I2: 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%–56.5%; I2: 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%–86.3%; I2: 91.6%, n: 1886). Interpretation: High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes. Funding: No funding was received

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases

International audienceBackgroundAmyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.Methods and findingsWe report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification.ConclusionsOur findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants

Green Edge ice camp campaigns: understanding the processes controlling the under-ice Arctic phytoplankton spring bloom

International audienceThe Green Edge initiative was developed to investigate the processes controlling the primary productivity and the fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797N, 63.7895W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea ice cover from the surface to the bottom at 360 m depth to better understand the factors driving the PSB. Key variables such as temperature, salinity, radiance, irradiance, nutrient concentrations, chlorophyll-a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, carbon stocks and fluxes were routinely measured at the ice camp. Here, we present the results of a joint effort to tidy and standardize the collected data sets that will facilitate their reuse in other Arctic studies. The dataset is available at http://www.seanoe.org/data/00487/59892/ (Massicotte et al., 2019a)

Previously unreported French families with AD-EOAD carrying an <i>APP</i> mutation.

<p>Previously unreported French families with AD-EOAD carrying an <i>APP</i> mutation.</p

Previously unreported French families with AD-EOAD and sporadic cases carrying a <i>PSEN1</i> mutation.

<p>Novel mutations appear in bold.</p

CSF biomarkers levels in mutation carriers (pg/mL).

<p>CSF biomarkers levels in mutation carriers (pg/mL).</p