Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

<p>Abstract</p> <p>Background</p> <p>The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.</p> <p>Methods</p> <p>We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term.</p> <p>Results</p> <p>Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management.</p> <p>Conclusions</p> <p>GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.</p

Results of the BiPo-1 prototype for radiopurity measurements for the SuperNEMO double beta decay source foils

The development of BiPo detectors is dedicated to the measurement of extremely high radiopurity in $^{208}$Tl and $^{214}$Bi for the SuperNEMO double beta decay source foils. A modular prototype, called BiPo-1, with 0.8 $m^2$ of sensitive surface area, has been running in the Modane Underground Laboratory since February, 2008. The goal of BiPo-1 is to measure the different components of the background and in particular the surface radiopurity of the plastic scintillators that make up the detector. The first phase of data collection has been dedicated to the measurement of the radiopurity in $^{208}$Tl. After more than one year of background measurement, a surface activity of the scintillators of $\mathcal{A}$($^{208}$Tl) $=$ 1.5 $\mu$Bq/m$^2$ is reported here. Given this level of background, a larger BiPo detector having 12 m$^2$ of active surface area, is able to qualify the radiopurity of the SuperNEMO selenium double beta decay foils with the required sensitivity of $\mathcal{A}$($^{208}$Tl) $<$ 2 $\mu$Bq/kg (90% C.L.) with a six month measurement.Comment: 24 pages, submitted to N.I.M.

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment

International audiencePURPOSE: Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC). METHODS: In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region. RESULTS: The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894). CONCLUSION: These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools

Data blinding for the nEDM experiment at PSI

Psychological bias towards, or away from, prior measurements or theory predictions is an intrinsic threat to any data analysis. While various methods can be used to try to avoid such a bias, e.g. actively avoiding looking at the result, only data blinding is a traceable and trustworthy method that can circumvent the bias and convince a public audience that there is not even an accidental psychological bias. Data blinding is nowadays a standard practice in particle physics, but it is particularly difficult for experiments searching for the neutron electric dipole moment (nEDM), as several cross measurements, in particular of the magnetic field, create a self-consistent network into which it is hard to inject a false signal. We present an algorithm that modifies the data without influencing the experiment. Results of an automated analysis of the data are used to change the recorded spin state of a few neutrons within each measurement cycle. The flexible algorithm may be applied twice (or more) to the data, thus providing the option of sequentially applying various blinding offsets for separate analysis steps with independent teams. The subtle manner in which the data are modified allows one subsequently to adjust the algorithm and to produce a re-blinded data set without revealing the initial blinding offset. The method was designed for the 2015/2016 measurement campaign of the nEDM experiment at the Paul Scherrer Institute. However, it can be re-used with minor modification for the follow-up experiment n2EDM, and may be suitable for comparable projects elsewhere

Central auditory processing in aging: The dichotic listening paradigm

International audienceObjectiveAging is associated with cognitive changing. Central auditory processing dysfunction may explain some understanding difficulties in elderly. It may be evaluated with the dichotic listening (DL) test, a widely-used experimental paradigm for studying inter-hemispheric interactions and attentional processes. This study examines central auditory language processing with a dichotic listening task in right-handed old subjects according to their age.DesignCross sectional-study.Settingmemory clinic and geriatric unit.ParticipantsAdult group (Ad) consisted in 26 subjects (21 women and 5 men) aged 50–69 years and an old adults group (Old-Ad) consisted in 20 subjects (19 women and 1 man) aged 70 to 89 years.MeasurementsDL consisted in a free-recall word task and a digit forced-attention task (forced-right: FR and forced-left: FL) in order to study central auditory language processing. In addition, we used neuropsychological tests to study executive functions and cognitive control, sustained by the prefrontal cortex.ResultsIn the free recall condition, we confirmed the classic right ear advantage (REA) in both groups, particularly in older subjects. In the forced condition, we observed an ear advantage with a change in ear asymmetry as a consequence of instruction: REA in FR and a left-ear advantage (LEA) in FL. We compared contaminations by the contra-lateral inattentive ear: reports of the left ear (LE) in the FR condition and reports of the right ear (RE) in the FL condition. Contaminations by the RE in the FL condition were more pronounced in Old-Ad suggesting difficulties in competition between the natural tendency for the RE and the instruction. In the Old-Ad group, the correlation between the RE score in FL and TMT B-A/A suggests an impairment in mental flexibility.ConclusionDL may be helpful to study central auditory dysfunction in aging. Our results suggest difficulties in attentional control and executive functions. Central auditory dysfunction should be evaluated in elderly because it potentially contributes to difficulty of hearing in noisy environment with consequences in the rehabilitation of presbyacousic subjects. More studies are needed to investigate the predictive value of DL as a marker of cognitive decline, particularly executive functions

Unveiling an exceptional zymogen: the single-chain form of tPA is a selective activator of NMDA receptor-dependent signaling and neurotoxicity

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Thrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia.

Cerebral ischemia is a pathology involving a cascade of cellular mechanisms, leading to the deregulation of proteostasis, including macroautophagy/autophagy, and finally to neuronal death. If it is now accepted that cerebral ischemia induces autophagy, the effect of thrombolysis/energy recovery on proteostasis remains unknown. Here, we investigated the effect of thrombolysis by PLAT/tPA (plasminogen activator, tissue) on autophagy and neuronal death. In two in vitro models of hypoxia reperfusion and an in vivo model of thromboembolic stroke with thrombolysis by PLAT/tPA, we found that ischemia enhances neuronal deleterious autophagy. Interestingly, PLAT/tPA decreases autophagy to mediate neuroprotection by modulating the PI3K-AKT-MTOR pathways both in vitro and in vivo. We identified IGF1R (insulin-like growth factor I receptor; a tyrosine kinase receptor) as the effective receptor and showed in vitro, in vivo and in human stroke patients and that PLAT/tPA is able to degrade IGFBP3 (insulin-like growth factor binding protein 3) to increase IGF1 (insulin-like growth factor 1) bioavailability and thus IGF1R activation.Abbreviations: AKT/protein kinase B: thymoma viral proto-oncogene 1; EGFR: epidermal growth factor receptor; Hx: hypoxia; IGF1: insulin-like growth factor 1; IGF1R: insulin-like growth factor I receptor; IGFBP3: insulin-like growth factor binding protein 3; Ka: Kainate; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK/ERK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; OGD: oxygen and glucose deprivation; OGD &lt;sub&gt;reox&lt;/sub&gt; : oxygen and glucose deprivation + reoxygentation; PepA: pepstatin A1; PI3K: phosphoinositide 3-kinase; PLAT/tPA: plasminogen activator, tissue; PPP: picropodophyllin; SCH77: SCH772984; ULK1: unc-51 like kinase 1; Wort: wortmannin