233 research outputs found
Broad white matter impairment in multiple system atrophy.
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p <â.001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought
NectarCAM : a camera for the medium size telescopes of the Cherenkov Telescope Array
NectarCAM is a camera proposed for the medium-sized telescopes of the
Cherenkov Telescope Array (CTA) covering the central energy range of ~100 GeV
to ~30 TeV. It has a modular design and is based on the NECTAr chip, at the
heart of which is a GHz sampling Switched Capacitor Array and a 12-bit Analog
to Digital converter. The camera will be equipped with 265 7-photomultiplier
modules, covering a field of view of 8 degrees. Each module includes the
photomultiplier bases, high voltage supply, pre-amplifier, trigger, readout and
Ethernet transceiver. The recorded events last between a few nanoseconds and
tens of nanoseconds. The camera trigger will be flexible so as to minimize the
read-out dead-time of the NECTAr chips. NectarCAM is designed to sustain a data
rate of more than 4 kHz with less than 5\% dead time. The camera concept, the
design and tests of the various subcomponents and results of thermal and
electrical prototypes are presented. The design includes the mechanical
structure, cooling of the electronics, read-out, clock distribution, slow
control, data-acquisition, triggering, monitoring and services.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
Novel imageânovel location object recognition task sensitive to age-related cognitive decline in nondemented elderly
Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel imageânovel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimerâs disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline
Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies
Several studies have confirmed the α-synuclein real-time quaking-induced conversion (RT-QuIC) assay to have high sensitivity and specificity for Parkinson's disease. However, whether the assay can be used as a robust, quantitative measure to monitor disease progression, stratify different synucleinopathies and predict disease conversion in patients with idiopathic REM sleep behaviour disorder remains undetermined. The aim of this study was to assess the diagnostic value of CSF α-synuclein RT-QuIC quantitative parameters in regard to disease progression, stratification and conversion in synucleinopathies. We performed α-synuclein RT-QuIC in the CSF samples from 74 Parkinson's disease, 24 multiple system atrophy and 45 idiopathic REM sleep behaviour disorder patients alongside 55 healthy controls, analysing quantitative assay parameters in relation to clinical data. α-Synuclein RT-QuIC showed 89% sensitivity and 96% specificity for Parkinson's disease. There was no correlation between RT-QuIC quantitative parameters and Parkinson's disease clinical scores (e.g. Unified Parkinson's Disease Rating Scale motor), but RT-QuIC positivity and some quantitative parameters (e.g. Vmax) differed across the different phenotype clusters. RT-QuIC parameters also added value alongside standard clinical data in diagnosing Parkinson's disease. The sensitivity in multiple system atrophy was 75%, and CSF samples showed longer T50 and lower Vmax compared to Parkinson's disease. All RT-QuIC parameters correlated with worse clinical progression of multiple system atrophy (e.g. change in Unified Multiple System Atrophy Rating Scale). The overall sensitivity in idiopathic REM sleep behaviour disorder was 64%. In three of the four longitudinally followed idiopathic REM sleep behaviour disorder cohorts, we found around 90% sensitivity, but in one sample (DeNoPa) diagnosing idiopathic REM sleep behaviour disorder earlier from the community cases, this was much lower at 39%. During follow-up, 14 of 45 (31%) idiopathic REM sleep behaviour disorder patients converted to synucleinopathy with 9/14 (64%) of convertors showing baseline RT-QuIC positivity. In summary, our results showed that α-synuclein RT-QuIC adds value in diagnosing Parkinson's disease and may provide a way to distinguish variations within Parkinson's disease phenotype. However, the quantitative parameters did not correlate with disease severity in Parkinson's disease. The assay distinguished multiple system atrophy patients from Parkinson's disease patients and in contrast to Parkinson's disease, the quantitative parameters correlated with disease progression of multiple system atrophy. Our results also provided further evidence for α-synuclein RT-QuIC having potential as an early biomarker detecting synucleinopathy in idiopathic REM sleep behaviour disorder patients prior to conversion. Further analysis of longitudinally followed idiopathic REM sleep behaviour disorder patients is needed to better understand the relationship between α-synuclein RT-QuIC signature and the progression from prodromal to different synucleinopathies
New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study
Objectives: Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. Methods: Assessment of OH during a 10â
min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6±8.8â
years; disease duration: 4.2±2.6â
years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. Results: 187 patients (54%) had moderate (>20â
mmâ
Hg (systolic blood pressure (SBP)) and/or >10â
mmâ
Hg (diastolic blood pressure (DBP)) or severe OH (>30â
mmâ
Hg (SBP) and/or >15â
mmâ
Hg (DBP)) within 3â
min and 250 patients (72%) within 10â
min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. Conclusions: This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10â
min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.Fil: Pavy Le Traon, Anne. University Hospital of Toulouse; Francia. Inserm; FranciaFil: Piedvache, A.. UniversitĂ© Paul Sabatier; FranciaFil: PĂ©rez Lloret, Santiago. University Hospital of Toulouse; Francia. Pontificia Universidad CatĂłlica Argentina "Santa MarĂa de los Buenos Aires". Instituto de Investigaciones BiomĂ©dicas. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas; ArgentinaFil: Calandra Buonara, G.. UniversitĂ di Bologna; Italia. Istituto delle Scienze Neurologiche di Bologna; ItaliaFil: Cochen De Cock, V.. University Hospital of Toulouse; Francia. University of Montpellier; FranciaFil: Colosimo, C.. Sapienza UniversitĂ di Roma; ItaliaFil: Cortelli, P.. UniversitĂ di Bologna; Italia. Istituto delle Scienze Neurologiche di Bologna; ItaliaFil: Debs, R.. University Hospital of Toulouse; FranciaFil: Duerr, S.. Universidad de Innsbruck; AustriaFil: Fanciulli, A.. Universidad de Innsbruck; AustriaFil: Foubert Samier, A.. Centre Hospitalier Universitaire de Bordeaux; Francia. Universite de Bordeaux; FranciaFil: Gerdelat, Angela. University Hospital of Toulouse; FranciaFil: Gurevich, T.. Tel-Aviv University; IsraelFil: Krismer, F.. Universidad de Innsbruck; AustriaFil: Poewe, W.. Universidad de Innsbruck; AustriaFil: Tison, Francois. Universite de Bordeaux; Francia. Centre Hospitalier Universitaire de Bordeaux; FranciaFil: Tranchant, C.. University Hospital Hautepierre; FranciaFil: Wenning, G.. Universidad de Innsbruck; AustriaFil: Meissner, Wassilios G.. Universite de Bordeaux; Francia. Centre Hospitalier Universitaire de Bordeaux; FranciaFil: Rascol, Olivier. University Hospital of Toulouse; Franci
Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter
We present a study of showers initiated by electrons, pions, kaons, and
protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE
scintillator-tungsten analogue hadronic calorimeter. The data were recorded at
the CERN Super Proton Synchrotron in 2011. The analysis includes measurements
of the calorimeter response to each particle type as well as measurements of
the energy resolution and studies of the longitudinal and radial shower
development for selected particles. The results are compared to Geant4
simulations (version 9.6.p02). In the study of the energy resolution we include
previously published data with beam momenta from 1 GeV to 10 GeV recorded at
the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table
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