Publications by authors named "Ralf A Linker"

Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system affecting approximately 2.8 million people worldwide. In addition to genetic and environmental factors, various lifestyle factors contribute to disease development and progression.

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  • The study investigates the impact of fingolimod treatment on heart rate (HR) and cardiovascular autonomic modulation in patients with relapsing-remitting multiple sclerosis (RRMS), particularly focusing on those who initially experienced prolonged HR slowing.
  • It involves monitoring 34 patients before and after fingolimod initiation, measuring various cardiovascular parameters to assess changes in autonomic function.
  • Findings indicate that while all patients experienced HR decreases after treatment, those with initial prolonged HR slowing showed persistent differences in HR and autonomic modulation six months later compared to those without this phenomenon.
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Background: Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet.

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  • Atrophy of both white and grey matter in the brains of people with multiple sclerosis (pwMS) occurs early and has significant clinical implications, which can be measured using MRI scans and automated software tools like "md brain."
  • This study looked at brain volumes from routine MRI scans of 53 pwMS, comparing those with higher disability scores (EDSS ≥ 3.5) and longer disease duration (≥ 10 years) to those with lower scores and shorter disease duration, as well as considering the impact of immunotherapy.
  • Results indicated that pwMS with higher EDSS scores and longer disease duration had notably smaller total brain and regional grey matter volumes, particularly in various lobes, and that those not receiving immunotherapy
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Magnetic resonance imaging (MRI) of the brain and spinal cord plays a crucial role in the diagnosis and monitoring of multiple sclerosis (MS). There is conclusive evidence that brain and spinal cord MRI findings in early disease stages also provide relevant insight into individual prognosis. This includes prediction of disease activity and disease progression, the accumulation of long-term disability and the conversion to secondary progressive MS.

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Genome-wide association studies identified a single nucleotide polymorphism (SNP) downstream of the transcription factor Sox8, associated with an increased risk of multiple sclerosis (MS). Sox8 is known to influence oligodendrocyte terminal differentiation and is involved in myelin maintenance by mature oligodendrocytes. The possible link of a Sox8 related SNP and MS risk, along with the role of Sox8 in oligodendrocyte physiology prompted us to investigate its relevance during de- and remyelination using the cuprizone model.

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The recent success of anti-CD20 monoclonal antibody therapies in the treatment of multiple sclerosis (MS) has highlighted the role of B cells in the pathogenesis of MS. In people with MS, the inflammatory characteristics of B-cell activity are elevated, leading to increased pro-inflammatory cytokine release, diminished anti-inflammatory cytokine production and an accumulation of pathogenic B cells in the cerebrospinal fluid. Rituximab, ocrelizumab, ofatumumab, ublituximab and BCD-132 are anti-CD20 therapies that are either undergoing clinical development, or have been approved, for the treatment of MS.

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Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death, resulting in functional disability. Remyelination is the natural repair process of demyelination, but it is often incomplete or fails in multiple sclerosis. Available therapies reduce the inflammatory state and prevent clinical relapses.

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Background And Objectives: Motor Neuron Diseases (MND) are rare diseases but have a high impact on affected individuals and society. This study aims to perform an economic evaluation of MND in Germany.

Methods: Primary patient-reported data were collected including individual impairment, the use of medical and non-medical resources, and self-rated Health-Related Quality of Life (HRQoL).

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  • Glioblastoma (GB) IDH-wildtype is a highly aggressive brain tumor that shows significant resistance to immunotherapy, with the translocator protein 18 kDa (TSPO) playing a key role in this process.* -
  • TSPO expression in GB cells correlates with immune infiltration and resistance to T cell-mediated killing, as it regulates apoptosis pathways and is upregulated in response to cytokines from T cells.* -
  • Targeting TSPO may enhance the effectiveness of immunotherapy for GB by overcoming intrinsic resistance mechanisms and improving the sensitivity of cancer cells to immune attacks.*
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  • FOXP3 regulatory T cells (Tregs) are crucial for preventing autoimmune responses, and their dysfunction can lead to autoimmunity with pro-inflammatory traits.
  • High salt (HS) exposure alters Treg metabolism, mimicking features seen in autoimmune Tregs by disrupting mitochondrial function.
  • The study suggests that short-term high salt intake can lead to long-lasting negative effects on Tregs, potentially increasing the risk of autoimmune conditions, but these effects may be reversible by targeting specific metabolic pathways.
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Borna disease virus 1 (BoDV-1) has been recognized as a rare cause of very severe encephalitis with rapid onset in central Europe. Data on cerebrospinal fluid (CSF) analysis have not yet been analyzed in detail. Here, we present the first study on CSF changes in BoDV-1 encephalitis.

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Background And Purpose: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain.

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Background: The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown.

Methods: Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing-remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission.

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Background: The use of antibiotics has been associated with increased risks of various cancers. Comprehensive information on the association of antibiotic use with the risk of glioma is lacking.

Methods: We performed a large case-control study based on the Clinical Practice Research Datalink (CPRD) GOLD from the United Kingdom.

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Background: Ozanimod, a sphingosine 1-phosphate receptor 1 and 5 modulator, was approved as a disease-modifying therapy for active relapsing-remitting multiple sclerosis (RRMS) in 2020 and for active ulcerative colitis in 2021. Long-term, real-world studies in a nonselective population are needed. OzEAN is an ongoing study to assess the real-world persistent use, effectiveness, and safety of ozanimod and its impact on quality of life (QoL) in patients with RRMS over a 5-year period.

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Mobile brain perfusion ultrasound (BPU) is a novel non-imaging technique creating only hemispheric perfusion curves following ultrasound contrast injection and has been specifically designed for early prehospital large vessel occlusion (LVO) stroke identification. We report on the first patient investigated with the SONAS system, a portable point-of-care ultrasound system for BPU. This patient was admitted into our stroke unit about 12 h following onset of a fluctuating motor aphasia, dysarthria and facial weakness resulting in an NIHSS of 3 to 8.

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Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas.

Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke.

Design, Setting, And Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks.

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Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10-15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study.

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Detecting the stroke etiology in young patients can be challenging. Among others, determining causality between ischemic stroke and patent foramen ovale (PFO) remains a complicated task for stroke neurologists, given the relatively high prevalence of PFOs. Thorough diagnostic workup to identify incidental vascular risk factors and rare embolic sources is crucial to avoid premature PFO closure suggesting successful secondary stroke prevention.

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Background: Sickle cell disease (SCD) is one of the most prevalent monogenetic diseases worldwide and one of the most serious complications is stroke. Transcranial Doppler (TCD) demonstrated to be highly predictive for an imminent stroke by measuring blood flow velocities in the basal cerebral arteries. Currently, the only curative therapy for SCD is hematopoietic stem cell transplantation (HSCT).

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Borna disease virus 1 (BoDV-1) causes rare but often fatal encephalitis in humans. Late diagnosis prohibits an experimental therapeutic approach. Here, we report a recent case of fatal BoDV-1 infection diagnosed on day 12 after hospitalization by detection of BoDV-1 RNA in the cerebrospinal fluid.

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Recently, oligodendrocytes (Ol) have been attributed potential immunomodulatory effects. Yet, the exact mode of interaction with pathogenic CNS infiltrating lymphocytes remains unclear. Here, we attempt to dissect mechanisms of Ol modulation during neuroinflammation and characterize the interaction of Ol with pathogenic T cells.

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Background: The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH).

Methods: Retrospective analyses and clinical follow-ups of individuals with at least mBC "possible" CAA from 2005 to 2018.

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Personalized medicine requires a patient-oriented approach with the exact classification of the disease being determined by the underlying pathophysiological processes. In particular, the optimal treatment of multiple sclerosis (MS) requires personalized treatment that goes beyond the pure concept of precision medicine; however, due to the lack of robust biomarkers beyond cranial magnetic resonance imaging and a lacking detailed understanding of some aspects of MS pathogenesis, this approach is not yet fully implemented. Important questions for a better therapeutic stratification of MS patients are: (1) when does MS start? (2) Does the spectrum of MS really span multiple diseases? (3) When does the progressive phase of the disease begin? (4) In which phase of the disease is there a therapeutic window for immunotherapy? Recent findings indicate that MS represents a spectrum of diseases and that there is a therapeutic delay of several years, on which the optimal treatment effect of a disease-modifying treatment depends.

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