Publications by authors named "Meuth S"

Background: Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.

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Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of this study was to investigate associations between IFSH and CSVD, and their potential repercussions, i.

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A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.

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Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients.

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For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice.

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Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.

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The human hippocampus is a key region in cognitive and emotional processing, but also a vulnerable and plastic region. Accordingly, there is a great interest in understanding how variability in the hippocampus' structure relates to variability in behavior in healthy and clinical populations. In this study, we aimed to link interindividual variability in subregional hippocampal networks (i.

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Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

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Article Synopsis
  • The study examined cognitive symptoms in individuals infected with SARS-CoV-2, finding that while most had mild respiratory symptoms, many also experienced cognitive issues like attention and memory deficits.
  • At baseline, those with SARS-CoV-2 showed higher fatigue levels compared to those who tested negative, but improvements in cognitive scores were noted in both groups over time.
  • Ultimately, the research highlights that even mild cases of COVID-19 can be linked to increased fatigue and cognitive challenges, reinforcing previous findings.
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Background: The reduction of processing times in the treatment of acute ischemic stroke is of outstanding importance. Our objective is to analyze the acute stroke care chain from onset to treatment in a city in Germany comprising three stroke units. Additionally, we discuss solutions for detected treatment delays.

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The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic and mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant.

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Objective: We examined the impact of the rs10191329 genetic risk variant on neuroaxonal damage as measured by serum neurofilament light chain (sNfL) levels, and disability progression in people with multiple sclerosis (pwMS).

Methods: In a cohort of pwMS (n = 740), 658 participants were prospectively monitored every 2 years for less than a decade while 82 of 740 pwMS were monitored retrospectively for up to 40 years. We investigated associations between rs10191329 variants and clinical outcome, including Expanded Disability Status Scale (EDSS), disability accrual (defined by EDSS-increase of at least 1.

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Article Synopsis
  • Advancements in molecular engineering have led to the development of CAR T-cell therapy, showing potential for treating various neurological disorders, including brain tumors and autoimmune conditions.
  • Although initial human trials for treating glioblastoma have had limited success, animal studies show promise for other conditions like multiple sclerosis and neuromyelitis optica spectrum disorders.
  • Innovative strategies using modified CAR T cells targeting autoreactive B cells are showing potential for treating autoimmune encephalitis, suggesting a hopeful future for CAR T-cell applications in neurology.
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Article Synopsis
  • B-cell-depletion with CD20 antibodies, specifically ocrelizumab (OCR) and ofatumumab (OFA), is an effective treatment for relapsing multiple sclerosis (RMS), but their comparative effectiveness in real-world settings was previously unknown.
  • A cohort study involving 1,138 RMS patients was conducted in Germany, using propensity-score matching to compare the outcomes of OCR and OFA treatment, focusing on clinical relapses, MRI lesion changes, and disability progression.
  • Results showed that OFA was non-inferior to OCR in overall effectiveness, but differences were noted in patients switching from other therapies, highlighting the need for more research on these specific cases.
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Background: The quality of treatment is especially critical in the context of complex and chronic diseases such as multiple sclerosis (MS). The Brain Health Initiative, an independent international consortium of neurologists, reached a consensus on time-based quality standards prioritizing brain health-focused care for people with MS.

Objectives: To gain deeper insights into the transferability of these quality standards to a specific area, we conducted a survey among MS experts across various MS centers in Germany.

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Article Synopsis
  • Long-term factor Xa (FXa) inhibition shows promise in reducing inflammation and improving outcomes after heart attacks and strokes by impacting platelet function.
  • In experiments with mice, chronic FXa inhibition led to smaller brain and heart injury sizes and better cardiac function compared to acute inhibition.
  • Analysis of patients revealed that those receiving FXa inhibitors had reduced infarct sizes and showed changes in platelet proteins that suggest decreased release of substances that promote inflammation and clotting.
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Background: Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment.

Methods: Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing-remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches.

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Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension.

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Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE) epitopes, intracellular (ALE) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE), and ALE without detectable antibodies (ALE). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE, 12 ALE, 28 ALE-GAD65, 37 ALE) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer's disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice.

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Article Synopsis
  • Eculizumab (ECU) has shown effectiveness in preventing attacks in patients with aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (NMOSDs) during a retrospective analysis in clinical settings between 2014 and 2022.
  • A total of 52 patients were studied, with 88% being attack-free during treatment, and the annualized attack rate significantly decreased from 1.0 to 0.
  • While common side effects included serious infections, five patients died from various complications, indicating a need for careful monitoring during long-term ECU therapy.
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Background: Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood.

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Background: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted.

Methods: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC).

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