Interferon-beta-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab

Background: Neuromyelitis optica (NMO) is a severely disabling inflammatory disorder of the central nervous system and is often misdiagnosed as multiple sclerosis (MS). There is increasing evidence that treatment options shown to be beneficial in MS, including interferon-β (IFN-β), are detrimental in NMO. Case presentation: We here report the first Caucasian patient with aquaporin 4 (AQP4) antibody (NMO-IgG)-seropositive NMO presenting with a tumefactive brain lesion on treatment with IFN-β. Disease started with relapsing optic neuritis and an episode of longitudinally extensive transverse myelitis (LETM) in the absence of any brain MRI lesions or cerebrospinal fluid-restricted oligoclonal bands. After initial misdiagnosis of multiple sclerosis (MS) the patient received subcutaneous IFN-β1b and, subsequently, subcutaneous IFN-β1a therapy for several years. Under this treatment, the patient showed persisting relapse activity and finally presented with a severe episode of subacute aphasia and right-sided hemiparesis due to a large T2 hyperintensive tumefactive lesion of the left brain hemisphere and a smaller T2 lesion on the right side. Despite rituximab therapy two further LETM episodes occurred, resulting in severe neurological deficits. Therapeutic blockade of the interleukin (IL)-6 signalling pathway by tocilizumab was initiated, followed by clinical and radiological stabilization. Conclusion: Our case (i) illustrates the relevance of correctly distinguishing NMO and MS since these disorders differ markedly in their responsiveness to immunomodulatory and -suppressive therapies; (ii) confirms and extends a previous report describing the development of tumefactive brain lesions under IFN-β therapy in two Asian NMO patients; and (iii) suggests tocilizumab as a promising therapeutic alternative in highly active NMO disease courses

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

Prevalence and prognostic value of neurological affections in hospitalized patients with moderate to severe COVID-19 based on objective assessments.

Neurological manifestations of coronavirus disease 2019 (COVID-19) have been frequently described. In this prospective study of hospitalized COVID-19 patients without a history of neurological conditions, we aimed to analyze their prevalence and prognostic value based on established, standardized and objective methods. Patients were investigated using a multimodal electrophysiological approach, accompanied by neuropsychological and neurological examinations. Prevalence rates of central (CNS) and peripheral (PNS) nervous system affections were calculated and the relationship between neurological affections and mortality was analyzed using Firth logistic regression models. 184 patients without a history of neurological diseases could be enrolled. High rates of PNS affections were observed (66% of 138 patients receiving electrophysiological PNS examination). CNS affections were less common but still highly prevalent (33% of 139 examined patients). 63% of patients who underwent neuropsychological testing (n = 155) presented cognitive impairment. Logistic regression models revealed pathology in somatosensory evoked potentials as an independent risk factor of mortality (Odds Ratio: 6.10 [1.01-65.13], p = 0.049). We conclude that hospitalized patients with moderate to severe COVID-19 display high rates of PNS and CNS affection, which can be objectively assessed by electrophysiological examination. Electrophysiological assessment may have a prognostic value and could thus be helpful to identify patients at risk for deterioration

G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic.

Funder: Pasteur Institute – Cenci Bolognetti FoundationFunder: Sapienza University of RomeFamilial encephalopathy with neuroserpin inclusion bodies (FENIB) is a progressive neurodegenerative disease caused by point mutations in the gene for neuroserpin, a serine protease inhibitor of the nervous system. Different mutations are known that are responsible for mutant neuroserpin polymerization and accumulation as inclusion bodies in many cortical and subcortical neurons, thereby leading to cell death, dementia and epilepsy. Many efforts have been undertaken to elucidate the molecular pathways responsible for neuronal death. Most investigations have concentrated on analysis of intracellular mechanisms such as endoplasmic reticulum (ER) stress, ER-associated protein degradation (ERAD) and oxidative stress. We have generated a HEK-293 cell model of FENIB by overexpressing G392E-mutant neuroserpin and in this study we examine trafficking and toxicity of this polymerogenic variant. We observed that a small fraction of mutant neuroserpin is secreted via the ER-to-Golgi pathway, and that this release can be pharmacologically regulated. Overexpression of the mutant form of neuroserpin did not stimulate cell death in the HEK-293 cell model. Finally, when treating primary hippocampal neurons with G392E neuroserpin polymers, we did not detect cytotoxicity or synaptotoxicity. Altogether, we report here that a polymerogenic mutant form of neuroserpin is secreted from cells but is not toxic in the extracellular milieu

Altered energy partitioning across terrestrial ecosystems in the European drought year 2018

Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO(2)exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands). Each component of the surface radiation and energy balance observed in 2018 was compared to available data per site during a reference period 2004-2017. Based on anomalies in precipitation and reference evapotranspiration, we classified 46 sites as drought affected. These received on average 9% more solar radiation and released 32% more sensible heat to the atmosphere compared to the mean of the reference period. In general, drought decreased net CO(2)uptake by 17.8%, but did not significantly change net evapotranspiration. The response of these fluxes differed characteristically between ecosystems; in particular, the general increase in the evaporative index was strongest in peatlands and weakest in croplands. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'

Statistical Analysis of Large Simulated Yield Datasets for Studying Climate Effects

Many studies have been carried out during the last decade to study the effect of climate change on crop yields and other key crop characteristics. In these studies, one or several crop models were used to simulate crop growth and development for different climate scenarios that correspond to different projections of atmospheric CO2 concentration, temperature, and rainfall changes (Semenov et al., 1996; Tubiello and Ewert, 2002; White et al., 2011). The Agricultural Model Intercomparison and Improvement Project (AgMIP; Rosenzweig et al., 2013) builds on these studies with the goal of using an ensemble of multiple crop models in order to assess effects of climate change scenarios for several crops in contrasting environments. These studies generate large datasets, including thousands of simulated crop yield data. They include series of yield values obtained by combining several crop models with different climate scenarios that are defined by several climatic variables (temperature, CO2, rainfall, etc.). Such datasets potentially provide useful information on the possible effects of different climate change scenarios on crop yields. However, it is sometimes difficult to analyze these datasets and to summarize them in a useful way due to their structural complexity; simulated yield data can differ among contrasting climate scenarios, sites, and crop models. Another issue is that it is not straightforward to extrapolate the results obtained for the scenarios to alternative climate change scenarios not initially included in the simulation protocols. Additional dynamic crop model simulations for new climate change scenarios are an option but this approach is costly, especially when a large number of crop models are used to generate the simulated data, as in AgMIP. Statistical models have been used to analyze responses of measured yield data to climate variables in past studies (Lobell et al., 2011), but the use of a statistical model to analyze yields simulated by complex process-based crop models is a rather new idea. We demonstrate herewith that statistical methods can play an important role in analyzing simulated yield data sets obtained from the ensembles of process-based crop models. Formal statistical analysis is helpful to estimate the effects of different climatic variables on yield, and to describe the between-model variability of these effects

Information Science in Europe

International audienceThis panel aims at giving an overview on the situation of information science in a few selected European countries/ regions (Scandinavia, France and former Yugoslavian countries). At the beginning the panelists will give an out- line on the discipline in their country. In particular the following questions will be addressed: * What is the state-of-the-art of information science with regard to academic education and research in your country? * How do you see the development in information science as a discipline in your country in the next five years? After the panelists have presented their opinion on the present and future situation on information science (see the following sections) they will continue with the discussion of the following topics: Is there anything like a European approach/identity on information science? If yes, what differentiations are there between Anglo- Saxon and European information science? With regard to the last two topics it is intended to engage the audience into the discussion as much as possible

SportsPose - A Dynamic 3D Sports Pose Dataset

Accurate 3D human pose estimation is essential for sports analytics, coaching, and injury prevention. However, existing datasets for monocular pose estimation do not adequately capture the challenging and dynamic nature of sports movements. In response, we introduce SportsPose, a large-scale 3D human pose dataset consisting of highly dynamic sports movements. With more than 176,000 3D poses from 24 different subjects performing 5 different sports activities, SportsPose provides a diverse and comprehensive set of 3D poses that reflect the complex and dynamic nature of sports movements. Contrary to other markerless datasets we have quantitatively evaluated the precision of SportsPose by comparing our poses with a commercial marker-based system and achieve a mean error of 34.5 mm across all evaluation sequences. This is comparable to the error reported on the commonly used 3DPW dataset. We further introduce a new metric, local movement, which describes the movement of the wrist and ankle joints in relation to the body. With this, we show that SportsPose contains more movement than the Human3.6M and 3DPW datasets in these extremum joints, indicating that our movements are more dynamic. The dataset with accompanying code can be downloaded from our website. We hope that SportsPose will allow researchers and practitioners to develop and evaluate more effective models for the analysis of sports performance and injury prevention. With its realistic and diverse dataset, SportsPose provides a valuable resource for advancing the state-of-the-art in pose estimation in sports.<br/