Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient

Les états de mal non convulsifs du sujet âgé (revue de la littérature et présentation de cinq cas)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Trouble bipolaire et troubles cognitifs (cas particulier des personnes âgées)

Le trouble bipolaire, défini par la survenue d épisodes thymiques dont au moins un épisode (hypo)maniaque ou mixte est désormais associé à une augmentation du risque de troubles cognitifs et de survenue de démence dont l origine est mal connue. Plusieurs facteurs sont incriminés : l évolution de la maladie psychiatrique, une pathologie dégénérative associée et l effet iatrogène des médicaments utilisés. Nous rapportons le cas d une patiente bipolaire de 80 ans suivie sur un plan psychiatrique et cognitif pendant deux ans nous permettant de discuter le rôle des différents facteurs impliqués dans la survenue de troubles cognitifs chez les personnes âgées bipolaires. Mais il nous apparaît important, aujourd hui, de procéder à des études de cohorte afin d établir la nature du lien entre les caractéristiques clinico thérapeutiques de la maladie et le déficit cognitif trait chez les patients âgés bipolaires et de pouvoir, à terme, améliorer la qualité de vie de ces patients.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Caractérisation des démences vasculaires sous-corticales (approche clinique et radiologique)

La démence vasculaire ischémique sous-corticale (DVSC) représente le sous-type le plus fréquent et le plus homogène de démence vasculaire. Elle est secondaire à une maladie des petites artères cérébrales et est associée à l IRM cérébrale à des hypersignaux de la substance blanche (HSB) en FLAIR et T2, des infarctus lacunaires et microsaignements. Le diagnostic de DVSC repose sur des critères dont la validité est discutée. Dans un échantillon de 115 sujets atteints de CADASIL (Cerebral Austosomal Dominant leukoencephalopathy Subcortical Infarcts), une maladie génétique représentant une forme pure de DVSC, nous avons montré que les critères spécifiques de DVSC avaient une meilleure sensibilité que les autres critères de DV. Chez 140 patients CADASIL, nous avons ensuite décrit le profil des troubles de mémoire épisodique verbale et montré qu il ne pouvait être considéré comme un marqueur spécifique des DVSC. Puis, dans un échantillon de 633 sujets âgés de 65 à 84 ans, autonomes et ayant des HSB, nous avons montré que la sévérité de ces lésions, le nombre ainsi que la localisation des infarctus lacunaires étaient des déterminants indépendants du déficit cognitif aux stades pré-démentiels de ces affections. Enfin, à partir de l étude de 66 sujets CADASIL ayant des HSB mais sans infarctus lacunaires, nous avons montré que les HSB étaient bien associés à une altération des fonctions cognitives mais n étaient responsables, seuls, d une démence. Nos résultats permettent de mieux comprendre les limites de l approche diagnostique des DV et suggère que des critères clinico-radiologiques plus fiables pourraient être proposés à des stades précoces de ces affectionsSubcortical ischemic vascular dementia (SIVD) is considered to be the most frequent and homogeneous subtype of vascular dementia. It is caused by various types of small vessel diseases and characterized by white matter hyperintensities (WMH), lacunar infarcts and microbleeds on brain MRI. In a group of 115 patients with CADASIL (Cerebral Autosomal Dominant Leukoencephalopathy Subcortical Infarcts), a genetic form of small vessel disease and a model of pure SIVD, we compared different sets of diagnostic criteria of vascular dementia and demonstrated that specific criteria of SIVD have a higher sensitivity, estimated to 90%, than general criteria of vascular dementia. In 140 CADASIL patients from the same cohort, we next described the patterns of verbal episodic memory impairment in this disease and showed their heterogeneity and showed that memory impairment pattern was a specific marker of SIVD. We then studied the MRI determinants of cognitive impairment associated with cerebral small vessel diseases. In a group of 633 non-disabled subjects, aged beyond 65 years-old and with WMH on MRI, we showed that the extent of WMH, as well as the number and the location of lacunar infarcts were independent determinants of cognitive impairment. Finally, in a group of 66 CADASIL patients with WMH but without any lacunar infarct, we found that CADASIL patients with isolated WMH can present with executive and attention deficit but not with dementia. Our work shows the limits of a diagnostic approach of vascular cognitive disorders based on the concept of dementia and suggests that more reliable criteria may be defined , but at earlier stages of cerebral small vessel diseasesPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Awareness of memory deficits in early stage Huntington's disease.

Patients with Huntington's disease (HD) are often described as unaware of their motor symptoms, their behavioral disorders or their cognitive deficits, including memory. Nevertheless, because patients with Parkinson's disease (PD) remain aware of their memory deficits despite striatal dysfunction, we hypothesize that early stage HD patients in whom degeneration predominates in the striatum can accurately judge their own memory disorders whereas more advanced patients cannot. In order to test our hypothesis, we compared subjective questionnaires of memory deficits (in HD patients and in their proxies) and objective measures of memory dysfunction in patients. Forty-six patients with manifest HD attending the out-patient department of the French National Reference Center for HD and thirty-three proxies were enrolled. We found that HD patients at an early stage of the disease (Stage 1) were more accurate than their proxies at evaluating their own memory deficits, independently from their depression level. The proxies were more influenced by patients' functional decline rather than by patients' memory deficits. Patients with moderate disease (Stage 2) misestimated their memory deficits compared to their proxies, whose judgment was nonetheless influenced by the severity of both functional decline and depression. Contrasting subjective memory ratings from the patients and their objective memory performance, we demonstrate that although HD patients are often reported to be unaware of their neurological, cognitive and behavioral symptoms, it is not the case for memory deficits at an early stage. Loss of awareness of memory deficits in HD is associated with the severity of the disease in terms of CAG repeats, functional decline, motor dysfunction and cognitive impairment, including memory deficits and executive dysfunction

Diagnostic criteria of vascular dementia in CADASIL

BACKGROUND AND PURPOSE - Subcortical ischemic vascular dementia (SIVD) is a major subtype of vascular dementia (VaD). Recently, the diagnostic criteria of VaD have been modified to encompass this entity. Application of these criteria in CADASIL, a genetic model of SIVD, may help to better assess their significance. The aim of this study was to compare different sets of diagnostic criteria of VaD in a population of CADASIL patients. METHODS - Different sets of diagnostic criteria of VaD (DSMIV, ICD10, standard NINDS-AIREN, modified NINDS-AIREN for SIVD) were applied to 115 CADASIL patients. Diagnosis of VaD was made through 2 steps: (1) diagnosis of dementia and (2) association of dementia to lesions of vascular origin. The percentage of patients satisfying the different sets and the concordance between these criteria was analyzed. RESULTS - At least 1 set of criteria was satisfied for diagnosis in 29 subjects with dementia. In this group of patients, the sensitivity of the DSM IV, ICD 10, and standard NINDS-AIREN criteria for VaD was, respectively, 79%, 72%, and 45%. In contrast, the sensitivity of the NINDS-AIREN criteria for SIVD was 90%. The incomplete sensitivity of these last criteria was related to the absence of focal signs in some patients. The neuroimaging criteria were satisfied in all patients with dementia. CONCLUSIONS - The modified NINDS-AIREN criteria of SIVD are the most sensitive VaD criteria in CADASIL. Among these criteria, the neuroimaging criteria, although poorly specific to dementia, have a complete sensitivity. In contrast, focal signs were inconstant in CADASIL patients with dementia

Relationship between awareness indexes and clinical variables.

<p>The Δ(subjHD-subjProx) index compares subjective ratings by patients and proxies. The Δ(subjHD-objHD) index compares subjective ratings by patients with objective memory performance. The Δ(subjProx-objHD) index compares subjective ratings by proxies and objective memory performance. HD1: patients at Stage 1, HD2: patients at Stage 2; HD1Prox: proxies of patients at Stage 1; HD2Prox: proxies of patients at Stage 2; FCSRT: Free and Cued Selective Reminding Test; RAVLT: Rey Auditory Verbal Learning Task; TFC: Total Functional Capacity; MDRS: Mattis Dementia Rating Scale; TMT-A; Trail Making Test form A; TMT-B: Trail Making Test form B; Stroop C/W: Stroop Color Interference Test; MCST: Modified Card Sorting Test; MADRS: Montgomery and Åsberg Depression Rating Scale. Only the values of Spearman's ρ are reported.</p>*<p>p<0.05;</p>**<p>p<0.01;</p>***<p>p<0.001.</p

Spearman correlations between subjective memory rating by HD patients and objective memory testing.

<p>HD1: patients at Stage 1, HD2: patients at Stage 2; FCSRT: Free and Cued Selective Reminding Test; RAVLT: Rey Auditory Verbal Learning Task. Total: sum of all responses; Global: global evaluation of memory; Remote: remote memory for personal events; Meta: metamemory. Only the values of Spearman's ρ are reported.</p>*<p>p<0.05;</p>**<p>p<0.01;</p>a<p>: 19/25;</p>b<p>: 14/21.</p

Awareness of memory deficits in Stage 1 but not in Stage 2 patients.

<p>Spearman correlations between objective memory performance and patients' subjective memory rating at Stage 1 and Stage 2. FCSRT-TFR: Free and Cued Selective Reminding Test - Total Free Recall; FCSRT-DFR: Free and Cued Selective Reminding Test - Delayed Free Recall.</p