468 results match your criteria: "Institute of Clinical Neuroimmunology[Affiliation]"

The degree and type of T cell infiltration influence rectal cancer prognosis regardless of classical tumor staging. We asked whether clonal expansion and tumor infiltration are restricted to selected-phenotype T cells; which clones are accessible in peripheral blood; and what the spatial distribution of their target antigens is. From five rectal cancer patients, we isolated paired tumor-infiltrating T cells (TILs) and T cells from unaffected rectum mucosa (T) using 13-parameter FACS single cell index sorting.

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with a modest concordance rate in monozygotic twins, which strongly argues for involvement of epigenetic factors. We observe highly similar peripheral blood mononuclear cell-based methylomes in 45 MS-discordant monozygotic twins. Nevertheless, we identify seven MS-associated differentially methylated positions (DMPs) of which we validate two, including a region in the TMEM232 promoter and ZBTB16 enhancer.

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Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis.

J Autoimmun

August 2019

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:02, 171 76, Stockholm, Sweden. Electronic address:

Article Synopsis
  • Autoreactive CD4 T-cells play a significant role in driving multiple sclerosis (MS), with myelin oligodendrocyte glycoprotein (MOG) being a key autoantigen, although its significance has been questioned due to low detection rates.
  • This study utilized a novel method with bead-bound MOG to analyze T-cell reactivity and found that a higher frequency of MOG-specific T-cells producing cytokines (IFNγ, IL-22, IL-17A) was present in individuals with MS compared to healthy controls.
  • Approximately 46.2-59.6% of MS patients exhibited MOG-reactivity, and blocking specific immune cells eliminated this response, indicating that MOG
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Huntington's disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive.

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Importance: Reliable biomarkers associated with disability worsening in multiple sclerosis (MS) are still needed.

Objective: To determine a possible association of intrathecal IgG synthesis and early disability worsening as measured by Expanded Disability Status Scale (EDSS) scoring in patients with relapsing-remitting MS or clinically isolated syndrome.

Design, Setting, And Participants: Cerebrospinal fluid measurements and clinical data from the observational longitudinal German national multiple sclerosis cohort were analyzed.

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Combining molecular intervention with in vivo imaging to untangle mechanisms of axon pathology and outgrowth following spinal cord injury.

Exp Neurol

August 2019

Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians University Munich, Munich 81377, Germany; Biomedical Center, Medical Faculty, Ludwig-Maximilians University Munich, Martinsried 82152, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany. Electronic address:

In vivo imaging of the spinal cord has allowed the observation of single axons over relatively long periods in the living mouse. After spinal cord injury, this methodology has helped to differentiate several pathological stages and tissue processes which impact axon morphology. In addition, the combination of in vivo imaging techniques with particular molecular intervention has shown that specific pathological axon changes can respond to distinct treatments.

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Staufen2 (Stau2) is an RNA-binding protein that is involved in dendritic spine morphogenesis and function. Several studies have recently investigated the role of Stau2 in the regulation of its neuronal target mRNAs, with particular focus on the hippocampus. Here, we provide evidence for Stau2 expression and function in cerebellar Purkinje cells.

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Four N-(E)-cinnamoyl (cinnamamide) derivatives of aminoalkanols with promising anticonvulsant and analgesic activity.

Bioorg Med Chem Lett

June 2019

Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.

Epilepsy and neuropathic pain are frequent neurological disorders with pathomechanism based on abnormal neuronal discharges. Secondary tissue impairment observed after traumatic brain injury is also connected with neuronal dysfunction. Those three neurological disorders are ineffectively treated with currently available pharmacotherapy options so great effort is made in searching for new effective drugs.

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MCC950 blocks enhanced interleukin-1β production in patients with NLRP3 low penetrance variants.

Clin Immunol

June 2019

Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximillian University, Munich, Germany.

Objective: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement.

Methods: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950.

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Risks and risk management in modern multiple sclerosis immunotherapeutic treatment.

Ther Adv Neurol Disord

April 2019

Department of Neurology with Institute of Translational Neurology, University of Münster, Building A1, Albert Schweitzer Campus 1, 48149 Münster, Germany.

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an 'optimal choice' for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations.

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Shared T cell receptor chains in blood memory CD4 T cells of narcolepsy type 1 patients.

J Autoimmun

June 2019

Centre de Physiopathologie Toulouse-Purpan (CPTP), Université de Toulouse, CNRS, Inserm, UPS, Toulouse, France. Electronic address:

Convergent evidence points to the involvement of T cells in the pathogenesis of narcolepsy type 1 (NT1). Here, we hypothesized that expanded disease-specific T cell clones could be detected in the blood of NT1 patients. We compared the TCR repertoire of circulating antigen-experienced CD4 and CD8 T cells from 13 recently diagnosed NT1 patients and 11 age-, sex-, and HLA-DQB1*06:02-matched healthy controls.

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Objective: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions.

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Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease.

Cells

January 2019

The Feinstein Institute for Medical Research, The Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Northwell Health System, Manhasset, NY 11030, USA.

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD).

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Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis.

Neuron

February 2019

Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians Universität München, Marchioninistraße 15, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians Universität München, Großhaderner Strasse 9, 82152 Planegg Martinsried, Germany; Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 Munich, Germany. Electronic address:

Axon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.

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The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are.

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Temporal evolution of acute multiple sclerosis lesions on serial sodium (Na) MRI.

Mult Scler Relat Disord

April 2019

Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address:

Background: Several studies have reported the characteristics of acute multiple sclerosis (MS) lesions on diffusion-weighted magnetic resonance imaging (DWI MRI). Current publications reported a transient reduction of the apparent diffusion coefficient (ADC) delineating an early phase of lesion evolution, before increased diffusion occurs in parallel to blood-brain-barrier (BBB) breakdown. Sodium MRI might provide another perspective on lesion development, but clinical applications have been limited to high field MR systems.

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High levels of antibodies against glutamic acid decarboxylase (GAD) are observed in patients with different neurological disorders, but cells producing these autoantibodies are largely unexplored. We detect circulating GAD-reactive B cells in peripheral blood that readily differentiate into antibody-producing cells. These cells are highly elevated in most patients with GAD-antibody-associated disorders (n = 15) compared to controls (n = 19).

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Magnetic Resonance Imaging Characteristics of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Clin Neuroradiol

June 2020

Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare hereditary disease presenting with distinct imaging features in middle-aged adults. This article describes the typical imaging features focusing on the longitudinal course of RVCL-S lesions.

Methods: In this study six subjects (five male, five related) with RVCL-S were retrospectively included from two university hospitals.

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Remyelination is a central aspect of new multiple sclerosis (MS) therapies, in which one aims to alleviate disease symptoms by improving axonal protection. However, a central problem is mediators expressed in MS lesions that prevent effective remyelination. Bone morphogenetic protein4 (BMP4) inhibits the development of mature oligodendrocytes in cell culture and also blocks the expression of myelin proteins.

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Managing Risks with Immune Therapies in Multiple Sclerosis.

Drug Saf

May 2019

Department of Neurology, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225, Düsseldorf, Germany.

Since the introduction of the interferons in the 1990s, a multitude of different immunomodulatory and immunosuppressant disease-modifying therapies for multiple sclerosis (MS) have been developed. They have all shown positive effects on clinical endpoints such as relapse rate and disease progression and are a heterogeneous group of therapeutics comprising recombinant pegylated and non-pegylated interferon-β variants, peptide combinations, monoclonal antibodies, and small molecules. However, they have relevant side effect profiles, which necessitate thorough monitoring and straightforward patient education.

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Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice.

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Acute frontal eye field infarction: A topodiagnostic challenge.

Neurology

January 2019

From the Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center (F.S.T.), and Department of Neurology (C.K., C.V., O.K., A.D.) and German Center for Vertigo and Balance Disorders (S.B., O.K.), University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany; and Institute of Neurology (C.K.), University College London, Queen Square, UK.

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Management and prognostic markers in patients with autoimmune encephalitis requiring ICU treatment.

Neurol Neuroimmunol Neuroinflamm

January 2019

Hans-Berger-Department of Neurology (J.S., D.B., C.G., O.W.W., A.G.), Jena University Hospital; Department of Neurology (H.B.H., S.T.G.), University Hospital Erlangen; Department of Neurology and Neurophysiology (H.F), University Hospital Freiburg; Department of Neurology (N.M., A.D.), University Hospital Münster; Department of Neurology (H.P., L.-T.L), Charité University Medicine Berlin; Department of Neurology (K.F.), Bezirksklinikum Regensburg; Neuroimmunology Section (F.L., G.N.), Institute of Clinical Chemistry and Department of Neurology, University Hospital Schleswig-Holstein, Kiel; Department of Neurology (I.S.), University Hospital Giessen; Center for Neurology and Psychiatrics (C.D.), University Hospital Köln; Department of Neurology (J.B.), University Hospital Heidelberg; Department of Neurology (J.B.), Klinikum Kassel; Department of Neurology (J.L.), University Hospital Ulm; Institute of Clinical Neuroimmunology (F.T.), Ludwig-Maximillians-University München; Department of Neurology (A.K.), Martha Maria Hospital Halle; Department of Neurology (A.J.), Dortmund Hospital; Department of Neurology (M.R.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (K.-W.S.), University Hospital Hannover; Department of Neurology (C.U.), Hospital Ludwigshafen; Institute of Medical Statistics, Computer and Data Sciences (A.S), Jena University Hospital; and Center for Sepsis Control and Care (A.S., C.G.), Jena University Hospital, Germany.

Article Synopsis
  • The study aimed to evaluate complications in ICU patients with autoimmune encephalitis (AE), their management, and factors affecting recovery outcomes.
  • It involved 120 patients across various hospitals, finding that many experienced severe issues like disorders of consciousness and sepsis, with mechanical ventilation being a major risk factor for poor recovery.
  • The findings suggest that common ICU complications are better predictors of outcomes than specific types of AE, highlighting the need for effective management and further research in this area.
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Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training.

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