The INSIGHT cohort: baseline analysis of structural MR imaging in asymptomatic subjects at risk for Alzheimer's disease

International audienc

Texture-based markers from structural imaging correlate with motor handicap in Parkinson’s disease

International audienceThere is a growing need for surrogate biomarkers for Parkinson's disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first-and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap

Lolita

Depuis sa parution, Lolita n’a cessé de susciter le questionnement parmi les chercheurs, pour les amener parfois, en bons lecteurs nabokoviens, à déceler, dans des effets peut-être fortuits, des procédés de style ou de codage. L’étude conjointe du film de Stanley Kubrick et du roman de Nabokov permet de mettre en perspective les spécificités de l’œuvre textuelle comme de l’œuvre filmique, et au-delà, de chacun des deux média. C’est aussi l’occasion d’explorer plus avant les outils et concepts d’analyse utilisés dans ces champs artistiques, certains s’appliquant aux deux, d’autres déportés de leur domaine d’origine pour enrichir celui d’arrivée lors d’une fertilisation croisée. Plus largement, c’est de représentation qu’il est question. Suivant l’injonction nabokovienne, lecteur, spectateur et critique se détournent de la perversion à laquelle d’aucuns voudraient réduire le contenu événementiel pour apprécier les formes diverses de la représentation, dont l’étonnante diversité dans le roman de Nabokov reçoit un éclairage nouveau par l’adjonction du film de Kubrick à l’étude.Lolita est un numéro spécial Agrégation 2010. Il met en ligne dans les meilleurs délais les textes critiques contribuant à la préparation du programme. Il pourrait être complété ultérieurement

Improved cerebral microbleeds detection using their magnetic signature on T2*-phase-contrast: a comparison study in a clinical setting

International audiencentroduction/Purpose: In vivo detection of cerebral microbleeds (CMBs) from T2* gradient recalled echo (GRE) magnitude image suffers from low specificity, modest inter-rater reproducibility and is biased by its sensitivity to acquisition parameters. New methods were proposed for improving this identification, but they mostly rely on 3D acquisitions, not always feasible in clinical practice. A fast 2D phase processing technique for computing internal field maps (IFM) has been shown to make it possible to characterize CMBs through their magnetic signature in routine clinical setting, based on 2D multi-slice acquisitions. However, its clinical interest for CMBs identification with respect to more common images remained to be assessed. To do so, systematic experiments were undertaken to compare the ratings obtained by trained observers with several image types, T2* magnitude, Susceptibility Weighted Imaging reconstructions (SWI) and IFM built from the same T2*-weighted acquisition.Materials/Methods: 15 participants from the MEMENTO multi-center cohort were selected: six subjects with numerous CMBs (20+/-6 CMBs), five subjects with a few CMBs (2 +/-1 CMBs) and four subjects without CMB. 2D multi-slice T2* GRE sequences were acquired on Philips and Siemens 3T systems. After pilot experiments, T2* magnitude, Susceptibility Weighted Imaging (SWI) minimum intensity projection (mIP) on three slices and IFM were considered for the rating experiments. A graphical user interface (GUI) was designed in order to consistently display images in random order. Six raters of various background and expertise independently selected “definite” or “possible” CMBs. Rating results were compared with respect to a specific consensus reference, on both lesion and subject type points of view.Results: IFM yielded increased sensitivity and decreased false positives rate (FPR) for CMBs identification compared to T2* magnitude and SWI-mIP images. Inter-rater variability was decreased with IFM when identifying subjects with numerous lesions, with only a limited increase in rating time. IFM thus appears as an interesting candidate to improve CMBs identification in clinical setting

Étude quantitative des anomalies de signal flair de la substance blanche dans les pathologies neurodégénératives

International audienceIntroduction. Au cours des dégénérescences lobaires fronto-temporales (DFT), et en particulier dans certaines formes génétiques, la présence d'hypersignaux flair de la substance blanche il a été rapporté dans les zones d'atrophie. Cependant, l'incidence et la spécificité de ces anomalies ne sont pas connues. L'objectif de ce travail était d'étudier le volume et la répartition topographique des hypersignaux flair de la substance blanche dans différentes pathologies neurodégénératives et de corréler ces anomalies aux données cliniques et aux patterns d'atrophie. Matériel et méthodes. Nous avons étudié 125 patients issus d'une cohorte rétrospective monocentrique, présentant un diagnostic de pathologie neurodégénérative (maladie d'Alzheimer, forme comportementale de DFT, démence sémantique, atrophie corticale postérieure, dégénérescence cortico-basale) ou de dépression. Tous les patients avaient eu une IRM cérébrale comprenant une acquisition 3DT1 et une séquence flair. Nous avons recueilli pour ces patients les données cliniques avec en particulier les facteurs de risques cardiovasculaires et le résultat des dosages des biomarqueurs de la maladie d'Alzheimer dans le liquide cérébrospinal. Le volume des hypersignaux de la substance blanche a été mesuré pour chaque patient sur la séquence flair à l'aide d'un algorithme de segmentation automatique (WHASA). Les volumes des différents lobes cérébraux ont été mesurés pour chaque patient à partir de la séquence 3DT1 par le logiciel Neuroreader (Horsens, Denmark). Résultats et conclusion. Les hypersignaux flair de la substance blanche dans les régions atrophiques ne sont pas spécifiques aux DFT, ils peuvent également être observés au cours des démences sémantiques et des atrophies corticales postérieures. Il est important de connaître ces anomalies, car elles ne doivent pas être prises à tort pour des séquelles vasculaires. Déclaration de liens d'intérêts. Jamila Ahdidan, Christian Christoffersen et Claus Pedersen sont employés par la société Brainreader commercialisant le logiciel Neuroreader

Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM’Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial

International audienceBackground: One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods: In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100-500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients' symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3-and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcome

Vladimir Nabokov et la France

L'ouvrage Vladimir Nabokov et la France explore un espace de recherche vaste et peu balisé : l'invention de la France dans l'œuvre de Nabokov et l'étude interdisciplinaire de son héritage français. L'écrivain russo-américain a entretenu avec la langue et la culture françaises une relation riche et intense dont la complexité se dévoile dans ce volume, qui ouvre un nouveau champ dans les études nabokoviennes à la croisée de plusieurs disciplines (études américaines, comparées, françaises et slaves) et de plusieurs forma­tions (linguistes, narratologues, philologues, traducteurs et artistes). Par-delà les considérations biographiques, cet ouvrage met en lumière la nature des liens à double sens entre la culture française et l'œuvre de l'écrivain, à savoir la place du cadre géographique et culturel de la France dans son œuvre, celle des écrivains et textes français, son usage de la langue française, sa relation à la pensée française, et enfin sa postérité dans le paysage littéraire et artistique français. De manière significative, le choix du bilinguisme pour les articles publiés ici vise à dépasser la division linguistique de la cri­tique nabokovienne en s'adressant aux lecteurs tant anglophones que francophones et, de manière plus profonde, à penser Nabokov dans les deux langues.À la mémoire de Samuel Schuman (1942-2014

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease

International audienceSeveral postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(ISQR)∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias

International audienceObjective : To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.Methods : We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology.Results : The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates.Conclusions: CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology

Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

Abstract Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT0192624