Anti-ARHGAP26 autoantibodies are associated with isolated cognitive impairment

Autoantibodies against the RhoGTPase-activating protein 26 (ARHGAP26) were originally identified in the context of subacute autoimmune cerebellar ataxia. Further studies identified a wider clinical spectrum including psychotic, affective, and cognitive symptoms. Only a few patients reported so far had evidence of a tumor association. A prospective analysis between January 2015 and December 2017 at the Dept. of Neurology at Charite-Universitatsmedizin Berlin identified 14 patients with ARHGAP26 autoantibodies on a cell-based assay, of which three patients had additional brain immunohistochemistry staining of cerebellar molecular layer and Purkinje cells, who were therefore considered antibody-positive. In all three patients, ARHGAP26 autoantibodies were associated with tumors. In two patients, an isolated cognitive impairment without additional neurological deficits was observed. These cases thus further extend the clinical spectrum associated with ARHGAP26 autoantibodies and strengthen a potential paraneoplastic context

Rabbit Anti T-Lymphocyte Globulin Induces Apoptosis in Peripheral Blood Mononuclear Cell Compartments and Leukemia Cells, While Hematopoetic Stem Cells Are Apoptosis Resistant

AbstractPolyclonal anti-T-lymphocyte globulins (ATG) are used in allogeneic stem cell transplantation (SCT) for the prophylaxis of graft versus host disease (GVHD) by in vivo T cell depletion. In this study we investigated the complement independent induction of apoptosis by rabbit ATG in peripheral blood mononuclear cell (PBMNC) compartments and hematopoetic stem cells (HSC). We also detected antileukemic activity of ATG by measuring apoptosis in myeloid and lymphatic leukemia cell lines and primary leukemia cells. We found ATG to induce apoptosis in T-lymphocytes (CD4+, CD8+), B-lymphocytes (CD20+), natural killer (NK)-cells (CD56+), and monocytes (CD14+). HSC, in contrast, were apoptosis resistant and could be growth stimulated by low-dose ATG in the presence of bystander cells. The human leukemia cell lines Jurkat, Daudi, DG-75 (lymphoblastic), and K562, HL-60, KG1, and U937 (myeloblastic) underwent ATG-induced apoptosis, whereas the NK-cell line YT was resistant. Primary leukemia cells from 6 investigated patients with acute lymphoblastic leukemia, 9 of 10 patients with chronic lymphocytic leukemia, and 4 of 8 patients with acute myeloblastic leukemia underwent ATG-induced apoptosis. We conclude apoptosis induction in all PBMNC compartments contributes to GVHD prophylaxis. ATG might support engraftment. Finally, antileukemic activity of ATG could positively influence the transplantation outcome

Artificial Intelligence in Process Engineering

In recent years, the field of Artificial Intelligence (AI) is experiencing a boom, caused by recent breakthroughs in computing power, AI techniques, and software architectures. Among the many fields being impacted by this paradigm shift, process engineering has experienced the benefits caused by AI. However, the published methods and applications in process engineering are diverse, and there is still much unexploited potential. Herein, the goal of providing a systematic overview of the current state of AI and its applications in process engineering is discussed. Current applications are described and classified according to a broader systematic. Current techniques, types of AI as well as pre- and postprocessing will be examined similarly and assigned to the previously discussed applications. Given the importance of mechanistic models in process engineering as opposed to the pure black box nature of most of AI, reverse engineering strategies as well as hybrid modeling will be highlighted. Furthermore, a holistic strategy will be formulated for the application of the current state of AI in process engineering

Anti-ARHGAP26 Autoantibodies Are Associated With Isolated Cognitive Impairment

Autoantibodies against the RhoGTPase-activating protein 26 (ARHGAP26) were originally identified in the context of subacute autoimmune cerebellar ataxia. Further studies identified a wider clinical spectrum including psychotic, affective, and cognitive symptoms. Only a few patients reported so far had evidence of a tumor association. A prospective analysis between January 2015 and December 2017 at the Dept. of Neurology at Charité—Universitätsmedizin Berlin identified 14 patients with ARHGAP26 autoantibodies on a cell-based assay, of which three patients had additional brain immunohistochemistry staining of cerebellar molecular layer and Purkinje cells, who were therefore considered antibody-positive. In all three patients, ARHGAP26 autoantibodies were associated with tumors. In two patients, an isolated cognitive impairment without additional neurological deficits was observed. These cases thus further extend the clinical spectrum associated with ARHGAP26 autoantibodies and strengthen a potential paraneoplastic context

E.U. paediatric MOG consortium consensus:Part 2 – Neuroimaging features of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Imaging plays a crucial role in differentiating the spectrum of paediatric acquired demyelinating syndromes (ADS), which apart from myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) includes paediatric multiple sclerosis (MS), aquaporin-4 antibody neuromyelitis optica spectrum disorders (NMOSD) and unclassified patients with both monophasic and relapsing ADS. In contrast to the imaging characteristics of children with MS, children with MOGAD present with diverse imaging patterns which correlate with the main demyelinating phenotypes as well as age at presentation. In this review we describe the common neuroradiological features of children with MOGAD such as acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, AQP4 negative NMOSD. In addition, we report newly recognized presentations also associated with MOG-ab such as the ‘leukodystophy-like’ phenotype and autoimmune encephalitis with predominant involvement of cortical and deep grey matter structures. We further delineate the features, which may help to distinguish MOGAD from other ADS and discuss the future role of MR-imaging in regards to treatment decisions and prognosis in children with MOGAD. Finally, we propose an MRI protocol for routine examination and discuss new imaging techniques, which may help to better understand the neurobiology of MOGAD.</p

Functional connectivity alterations between default mode network and occipital cortex in patients with obsessive-compulsive disorder (OCD)

Altered brain network connectivity is a potential biomarker for obsessive-compulsive disorder (OCD). A meta-analysis of resting-state MRI studies by Gürsel et al. (2018) described altered functional connectivity in OCD patients within and between the default mode network (DMN), the salience network (SN), and the frontoparietal network (FPN), as well as evidence for aberrant fronto-striatal circuitry. Here, we tested the replicability of these meta-analytic rsfMRI findings by measuring functional connectivity during resting-state fMRI in a new sample of OCD patients (n = 24) and matched controls (n = 33). We performed seed-to-voxel analyses using 30 seed regions from the prior meta-analysis. OCD patients showed reduced functional connectivity between the SN and the DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, nor FPN. Additionally, we observed reduced connectivity between the visual network to both the DMN and SN in OCD patients, in particular reduced functional connectivity between lateral parietal seeds and the left inferior lateral occipital pole. Furthermore, the right lateral parietal seed (associated with the DMN) was more strongly correlated with a cluster in the right lateral occipital cortex and precuneus (a region partly overlapping with the Dorsal Attentional Network (DAN)) in patients. Importantly, this latter finding was positively correlated to OCD symptom severity. Overall, our study partly replicated prior meta-analytic findings, highlighting hypoconnectivity between SN and DMN as a potential biomarker for OCD. Furthermore, we identified changes between the SN and the DMN with the visual network. This suggests that abnormal connectivity between cortex regions associated with abstract functions (transmodal regions such as the DMN), and cortex regions associated with constrained neural processing (unimodal regions such as the visual cortex), may be important in OCD

No Impact of Functional Connectivity of the Motor System on the Resting Motor Threshold: A Replication Study

The physiological mechanisms of corticospinal excitability and factors influencing its measurement with transcranial magnetic stimulation are still poorly understood. A recent study reported an impact of functional connectivity (FC) between the primary motor cortex (M1) and the dorsal premotor cortex (PMd) on the resting motor threshold (RMT) of the dominant hemisphere. We aimed to replicate these findings in a larger sample of 38 healthy right-handed subjects with data from both hemispheres. Resting-state FC was assessed between the M1 and five a priori defined motor-relevant regions on each hemisphere as well as interhemispherically between both primary motor cortices. Following the procedure by the original authors, we included age, cortical gray matter volume, and coil-to-cortex distance (CCD) as further predictors in the analysis. We report replication models for the dominant hemisphere as well as an extension to data from both hemispheres and support the results with Bayes factors. FC between the M1 and the PMd did not explain the variability in the RMT, and we obtained moderate evidence for the absence of this effect. In contrast, CCD could be confirmed as an important predictor with strong evidence. These findings contradict the previously proposed effect, thus questioning the notion of the PMd playing a major role in modifying corticospinal excitability

Clinical and neuroimaging findings in MOGAD–MRI and OCT

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are rare in both children and adults, and have been recently suggested to be an autoimmune neuroinflammatory group of disorders that are different from aquaporin-4 autoantibody-associated neuromyelitis optica spectrum disorder and from classic multiple sclerosis. In-vivo imaging of the MOGAD patient central nervous system has shown some distinguishing features when evaluating magnetic resonance imaging of the brain, spinal cord and optic nerves, as well as retinal imaging using optical coherence tomography. In this review, we discuss key clinical and neuroimaging characteristics of paediatric and adult MOGAD. We describe how these imaging techniques may be used to study this group of disorders and discuss how image analysis methods have led to recent insights for consideration in future studies