Antineuronale Autoimmunenzephalitis

Vor etwa 10 Jahren wurde eine neue Kategorie von Autoimmunenzephalitiden entdeckt, die durch Autoantikörper gegen synaptische oder Oberflächenantigene verursacht werden und in der psychiatrischen Praxis von hoher Relevanz sind. Insbesondere bei subakuter Psychose, Gedächtnisstörungen und einer Kombination psychiatrischer und neurologischer Symptome sollten die Autoimmunenzephalitiden in die Differenzialdiagnose eingeschlossen werden. Mit der Testung von Liquor und/oder Serum in einem spezialisierten Labor können die bekannten Antikörper innerhalb weniger Tage detektiert werden. Eine frühe Diagnose und rasche Immuntherapie führen in den meisten Fällen zu einer Remission der Symptome.Approximately 10 years ago, a new category of autoimmune encephalitis was described that is caused by autoantibodies against synaptic or surface antigens and has a high relevance for psychiatric care. In particular, in cases of subacute psychosis, memory deficit, and combination of neurological and psychiatric symptoms, the differential diagnoses should include autoimmune encephalitis. In a specialized lab, the known antibodies can be detected in cerebrospinal fluid and/or serum within a couple of days. Early diagnosis and immunotherapy are crucial for a favorable outcome and lead in most cases to complete remission.(VLID)353202

Religiöse Tradition in Bewegung: Zur Hermeneutik des Zweiten Vatikanischen Konzils im jüdisch-christlichen Dialog

Traditionen sind dynamisch und vielgestaltig. Die Haltung der Kirche zum Judentum erfuhr durch das Zweite Vatikanische Konzil mit der Erklärung Nostra aetate eine positive Wende. Wie können diese tiefgreifenden Veränderungen und die hier beobachtbare Traditionsdynamik beschrieben und gedeutet werden? Die Autorin eröffnet durch eine dekonstruktive und kulturwissenschaftlich reflektierte theologische Traditionstheorie einen neuen Blick auf kirchliche und religiöse Traditionen. Die entworfene dialogsensible Traditionshermeneutik und Rezeptionstheorie bieten Deutungsalternativen zu Polarisierungen wie Bruch und Kontinuität und leisten einen Beitrag zu einer interdisziplinären Theologie

Carbonic anhydrase-related protein VIII antibodies and paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a common cause of subacute cerebellar ataxia caused by widespread loss of the Purkinje cells of the cerebellum. PCD diagnosis can be confirmed by detection of onconeural antibodies that may also indicate the underlying tumour type 1. Most onconeural antibodies associated with PCD recognize intracellular antigens in Purkinje cells 2. These antigens are supposed to induce, besides the antibody synthesis, an antigen‐specific cytotoxic T‐cell attack that probably is responsible of the Purkinje cell death and limited response to treatment 3, 4. The most common onconeural antibody in PCD is the Yo antibody that associates with breast and ovarian cancer 4. In a previous case report, we identified a new antibody, targeting the intracellular Purkinje cell protein carbonic anhydrase‐related protein VIII (CARP VIII), in a patient with PCD and melanoma 5. We provide further evidence for the association of CARP VIII antibodies with PCD by demonstrating a second patient with these antibodies, who had an ovarian adenocarcinoma and developed cerebellar ataxia

Antibody repertoire in paraneoplastic cerebellar degeneration and small cell lung cancer

The goal of this study is to determine whether patients with paraneoplastic cerebellar degeneration (PCD) and small-cell lung cancer (SCLC) have a specific repertoire of antibodies, if SOX1 antibodies (SOX1-ab) can predict the presence of SCLC, and if antibodies to cell surface antigens occur in this syndrome. Antibody analysis was done using immunohistochemistry on rat brain, immunoblot with recombinant antigens, screening of cDNA expression libraries, and immunolabeling of live neurons in 39 patients with PCD and SCLC. VGCC-ab were measured by RIA, and SOX1-ab, Hu-ab, and ZIC4-ab by immunoblot. Lambert-Eaton myastenic syndrome (LEMS) was present in 10 of 23 patients with electrophysiological studies. At least one antibody was detected in 72% of patients. The individual frequencies were: 49% SOX1-ab, 44% VGCC-ab, 31% Hu-ab, and 13% ZIC4-ab. SOX1-ab occurred in 76% of patients with VGCC-ab and 27% of those without VGCC-ab (p = 0.0036). SOX1-ab were not found in 39 patients with sporadic late-onset cerebellar ataxia, 23 with cerebellar ataxia and glutamic acid decarboxylase antibodies, and 73 with PCD and cancer types other than SCLC (31 without onconeural antibodies, 25 with Yo-ab , 17 with Tr-ab). Five patients (13%) had antibodies against unknown neuronal cell surface antigens but none of them improved with immunotherapy. One serum immunoreacted against the axon initial segment of neurons and another serum against ELKS1, a protein highly expressed in the cerebellum that interacts with the beta4-subunit of the VGCC. In conclusion, 72% of patients with PCD and SCLC had one or more antibodies that indicate the presence of this tumor. In these patients, VGCC-ab and SOX1-ab occur tightly associated. SOX1-ab are predictors of SCLC in ataxia patients with a specificity of 100% and sensitivity of 49%. Unlike limbic encephalitis with SCLC, antibodies to cell surface antigens other than VGCC-ab, are infrequent and do not predict response to treatment

International Journal of Molecular Sciences / Subcellular sequestration and impact of heavy metals on the ultrastructure and physiology of the multicellular freshwater alga Desmidium swartzii

Due to modern life with increasing traffic, industrial production and agricultural practices, high amounts of heavy metals enter ecosystems and pollute soil and water. As a result, metals can be accumulated in plants and particularly in algae inhabiting peat bogs of low pH and high air humidity. In the present study, we investigated the impact and intracellular targets of aluminum, copper, cadmium, chromium VI and zinc on the filamentous green alga Desmidium swartzii, which is an important biomass producer in acid peat bogs. By means of transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) it is shown that all metals examined are taken up into Desmidium readily, where they are sequestered in cell walls and/or intracellular compartments. They cause effects on cell ultrastructure to different degrees and additionally disturb photosynthetic activity and biomass production. Our study shows a clear correlation between toxicity of a metal and the ability of the algae to compartmentalize it intracellularly. Cadmium and chromium, which are not compartmentalized, exert the most toxic effects. In addition, this study shows that the filamentous alga Desmidium reacts more sensitively to aluminum and zinc when compared to its unicellular relative Micrasterias, indicating a severe threat to the ecosystem.(VLID)156767

XR-Supported Communication in Green Urban Projects. Participating in Urban Change through Virtual and Augmented Reality

Public participation in urban planning and design processes is becoming increasingly important in European cities to improve transparency, enhance decision-making, and encourage community engegamenent. However, broad and inclusive participation faces a number of significant challenges. Typical participation processes rely on face-to-face interaction and are only able to reach small and non-representative groups of people. To this day, direct means of communication are important because of the high complexity of urban planning and design tasks and the multi-faceted demands on urban spaces, which can hardly be represented in online questionnairs and one-way information campaigns. Additionally, urgent measures to reduce heat in cities and to counteract other negative effects of the climate crisis need to be explained to gain the support of local communities. These challenges are often compounded by low budgets for participation processes and a lack of commitment to a thorough communication strategy. Over the past few decades, new information and communication technologies have radically changed the way we communicate. The advent of smartphones and the institutionalization of the internet have made it possible to interact with many people simultaneously in real time and at a low cost. Today, powerful mobile devices and the emergence of virtual and augmented reality applications promise new ways to communicate spatial change and to interact with the urban environment. The exploitation of these new technologies to support climate-friendly urban design projects with broad public participation was the declared goal of the Green Living Augmented+virtual ReAlity (GLARA) research and development project. At the heart of the project was the development of the GLARA app, a mobile application that visualizes the spatial and microclimatic effects of urban design projects. Choosing between the virtual and augmented reality modes, users could explore the altered urban space from home or directly in the respective public space. In the latter case, the live image of the mobile phone camera (image of reality) was overlaid with 3D elements like trees, benches and more. This type of vizualisation provided a unique spatial experience of the proposed design project. At the same time, the results of a micro-climate simulation, which shows the effects on surface temperature, perceived temperature, and wind was visualized and made tangible via the app. Last but not least, the application allowed users to provide feedback on the design from anywhere at any time, decoupling participation from the need to be physically present at a specific place and time and allowing a wider range of people to contribute their opinions to the planning process. The GLARA app was combined with a selected set of face-to-face participation tools to form a holisitc participatory planning service for open spaces with green infrastructure. The full GLARA service was tested in a case study in Vienna’s 7th district, Neubau. The local district administration had plans to redesign a narrow residential street in the course of laying new water pipes. The GLARA team accompanied the planning process over a period of one and a half years with a balanced mix of analogue and digital participation tools including the GLARA app. The introduction of a second participation loop based on the preliminary landscape design for the street was a novelty for the administration but was well received by the participating residents. The design was visualized via the app and offered an immersive experience of future spatial change. However, a number of technical and practical challenges remain for future development of the app, including better ways for device localisation, operability on less powerful mobile devices, reducing the effort required to create the 3D visualisations, and further reducing barriers for less tech-savvy populations

Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica

Neuromyelitis optica (NMO) is an autoimmune disease targeting aquaporin 4 (AQP4), localized mainly at the astrocytic foot processes. Loss of AQP4 and glial fibrillary acidic protein (GFAP) was reported, but the pathological significance of astrocytopathy is still controversial. Here we show that active lesions in NMO display a wide spectrum of pathology even within a single tissue block of an individual patient. We have distinguished six different lesion types. The first reflects complement deposition at the surface of astrocytes, associated with granulocyte infiltration and astrocyte necrosis and followed by demyelination, global tissue destruction and the formation of cystic, necrotic lesions (lesion type 2). Such destructive lesions lead to Wallerian degeneration in lesion-related tracts (lesion type 3). Around active NMO lesions AQP4 may selectively be lost in the absence of aquaporin 1 (AQP1) loss or other structural damage (lesion type 4). Another pattern is characterized by clasmatodendrosis of astrocytes, defined by cytoplasmic swelling and vacuolation, beading and dissolution of their processes and nuclear alterations resembling apoptosis, which was associated with internalization of AQP4 and AQP1 and astrocyte apoptosis in the absence of complement activation. Such lesions give rise to extensive astrocyte loss, which may occur in part in the absence of any other tissue injury, such as demyelination or axonal degeneration (lesion type 5). Finally, lesions with a variable degree of astrocyte clasmatodendrosis are found, which show plaque-like primary demyelination that is associated with oligodendrocyte apoptosis, but with preservation of axons (lesion type 6). In active multiple sclerosis (MS) lesions astrocytes reveal changes of reactive protoplasmatic or fibrillary gliosis. Only in a subset of lesions, in patients with aggressive disease, loss of AQP4 is observed in the initial stage of their formation, which is associated with retraction of astrocyte processes in the absence of complement deposition, granulocyte infiltration or loss of AQP1 or astrocytes. Our data underline the primary assault of astrocytes in NMO lesions, but also indicate that different mechanisms of tissue injury operate in parallel in the same patient and even within the same lesion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1116-7) contains supplementary material, which is available to authorized users

An optimized immunohistochemistry technique improves NMO-IgG detection: study comparison with cell-based assays

Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection

Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients

Over the last years the clinical picture of autoimmune encephalitis has gained importance in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Early diagnosis and the initiation of the appropriate treatment is the most relevant step in the management of the patients. Over the last years advances in neuroimmunology have elucidated pathophysiological basis and improved treatment concepts. In this monocentric study we compare demographics, diagnostics, treatment options and outcomes with knowledge from literature. We present 38 patients suffering from autoimmune encephalitis. Antibodies were detected against NMDAR and LGI1 in seven patients, against GAD in 6 patients) one patient had coexisting antibodies against GABAA and GABAB), against CASPR2, IGLON5, YO, Glycine in 3 patients, against Ma-2 in 2 patients, against CV2 and AMPAR in 1 patient; two patients were diagnosed with hashimoto encephalitis with antibodies against TPO/TG. First, we compare baseline data of patients who were consecutively diagnosed with autoimmune encephalitis from a retrospective view. Further, we discuss when to stop immunosuppressive therapy since how long treatment should be performed after clinical stabilization or an acute relapse is still a matter of debate. Our experiences are comparable with data from literature. However, in contrary to other experts in the field we stop treatment and monitor patients very closely after tumor removal and after rehabilitation from first attack