Ralf A Linker's research while affiliated with University Hospital Regensburg and other places

Publications (384)

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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. We identified 442...
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The clinical course of multiple sclerosis (MS) is highly variable among patients, thus creating important challenges for the neurologist to appropriately treat and monitor patient progress. Despite some patients having apparently similar symptom severity at MS disease onset, their prognoses may differ greatly. To this end, we believe that a proacti...
Article
Introduction: Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addre...
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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...
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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-...
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The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinica...
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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 endov...
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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 seronegativ...
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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...
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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 sour...
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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. In a retrospective analysis, we detect BoDV-1 RNA 1...
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Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) o...
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Background The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical t...
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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. RNA expression anal...
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BACKGROUND Mutation of isocitrate dehydrogenase (IDH) is not only an important landmark in the development of low-grade gliomas, but also has prognostic significance and is a potential therapeutic target. There is a high need to determinate IDH mutation status at diagnosis and during the course of therapy in a non-invasive and reliable manner. We e...
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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-u...
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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...
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Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course...
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Zusammenfassung Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung...
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Background: Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions. Purpose: To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS relapse and during recovery. Study type: Prospective. Subjects: Twenty-nine relapsing-remitting MS patients with an acute relapse were included....
Article
Significance Our data add to the recently identified importance of the skin as a storage compartment of sodium. We found a higher sodium MRI ( ²³ Na-MRI) signal in the skin of male multiple sclerosis (MS) patients compared to matched healthy controls as well as in the animal model, experimental autoimmune encephalomyelitis. Considering the salt eff...
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Goal: Cerebral amyloid angiopathy (CAA) is a frequent cause of atypical intracerebral hemorrhage (ICH) in the elderly. Stroke risk factors such as arterial hypertension (AHT), atrial fibrillation (AFib), diabetes mellitus (DM), and renal dysfunction (RD) are increasingly apparent in these patients. In this retrospective study, we analyzed the prese...
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the c...
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High-fat diets (HFD) are linked to obesity and associated comorbidities and induce pathogenic T helper (Th) 17 cells while decreasing regulatory T cells (Treg). This pro-inflammatory environment also aggravates immunopathology in experimental autoimmune encephalomyelitis (EAE) as a prototype model of T cell mediated autoimmunity. The strong associa...
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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that is characterised pathologically by demyelination, gliosis, neuro-axonal damage and inflammation. Despite intense research, the underlying pathomechanisms driving inflammatory demyelination in MS still remain incompletely understood. It is thought to b...
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Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questio...
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Background: The COVID-19 pandemic lockdown (CPL) lead to a significant decrease in emergency admissions worldwide. We performed a timely analysis of ischemic stroke (IS) and related consultations using the telestroke TEMPiS "working diagnosis" database prior (PL), within (WL), and after easing (EL) of CPL. Methods: Twelve hospitals were selected...
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Background and purpose Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. Patients and methods Twenty...
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Multiple sclerosis (MS) disease risk is associated with reduced sunexposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (nNationMS = 946, nBIONAT = 990). Additionally, effect-modification by medication and photosensitivityassocia...
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Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of I...
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Recent literature indicates a potential importance of the gut microbiota for immune‐mediated diseases. For instance, decreased diversity of commensals or an outgrowth of some bacterial strains, referred to as gut dysbiosis, was recently linked to hypertension, colitis, lupus, rheumatoid arthritis, and multiple sclerosis (MS). Studies in experimenta...
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The transition from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS) remains a clinical challenge owing to the heterogeneous course of the disease, indistinct disease progression and lack of availability of validated biomarkers and diagnostic tools. This article summarizes the outcomes from an international...
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Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, direc...
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Stroke-associated pneumonia is a major cause for poor outcomes in the post-acute phase after stroke. Several studies have suggested potential links between neglected oral health and pneumonia. Therefore, the aim of this prospective observational study was to investigate oral health and microbiota and incidence of pneumonia in patients consecutively...
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Optic nerve sheath diameter (ONSD) sonography is a reliable method for evaluation of intracranial pressure, yet there is a lack of reliable normal values. In the study described here, we established normal ONSD values in three different age groups and both sexes. One hundred eighty-seven volunteers without central nervous system disease were enroll...
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Objective In this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS)....
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Background During the COVID-19 pandemic emergency departments have noted a significant decrease in stroke patients. We performed a timely analysis of the Bavarian telestroke TEMPiS “working diagnosis” database. Methods Twelve hospitals from the TEMPiS network were selected. Data collected for January through April in years 2017 through 2020 were e...
Preprint
Background: Multiple sclerosis (MS) disease risk is associated with reduced sun exposure. This study assessed the relationship between measures of sun-exposure (vitamin D (vitD), latitude) and MS disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants. Methods: Two multi-center...
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Objective: Pre-hospital stroke scales imperfectly distinguish between acute ischemic stroke including large intracranial vessel occlusion, hemorrhagic stroke, and stroke mimics. Current point-of-care diagnostics include serum biomarkers, telemedicine, mobile computed tomography units and ultrasound equipment. The aim of our study was to evaluate a...
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Introduction Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis. A full treatment course comprises two treatment cycles given with 1 year of intermission. Further dosing is not routinely recommended in years 3 and 4. Areas covered The long-term management of patients treat...
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Neuroinflammation and demyelination are hallmarks of several neurological disorders such as multiple sclerosis and multiple system atrophy. To better understand the underlying mechanisms of de- and regeneration in respective diseases, it is critical to identify factors modulating these processes. One candidate factor is alpha-Synuclein (aSyn), whic...
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Objective To assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). Methods This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nuc...
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BACKGROUND AND PURPOSE Long‐term surveillance of intracranial pressure (ICP) in neurological/neurosurgical patients during ventilator weaning and early neurorehabilitation currently relies on clinical observation because neuroimaging is rarely readily available. In this prospective study, multimodal neurosonography and pupillometry are evaluated fo...
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Background Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a “real-world” setting. Methods In t...
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Background We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. Methods In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated synd...
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The conversion of relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) cannot be defined by a sharp threshold determined by event-based measures, but rather represents a gradual process. In consequence, there may exist a transitional phase between RRMS and clearly established SPMS. So far, transitional MS has been poorly...
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Lumbar puncture (LP) is commonly used in the diagnostic workup of neurological patients, often to exclude inflammatory diseases of the central nervous system. In clinical practice, an increase of white blood cell count (WBC) in the cerebrospinal fluid (CSF) after a LP is often assumed as reactive to the first puncture. Scientific evidence of this h...
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Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determ...
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During neuroinflammation, the shaker type potassium channel Kv1.4 is re-expressed in oligodendrocytes (Ol), but not immune cells. Here, we analyze the role of endogenous Kv1.4 in two demyelinating animal models of multiple sclerosis. While Kv1.4 deficiency in primary murine Ol led to a decreased proliferation rate in vitro, it did not exert an effe...
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Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particul...
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ZUSAMMENFASSUNG Die Multiple Sklerose (MS) ist eine autoimmunvermittelte Erkrankung des zentralen Nervensystems (ZNS), die in Deutschland ca. 230000 Menschen betrifft. Bis heute existiert für die MS keine Heilung. Als Ursachen werden genetische und Umwelt-Risikofaktoren angenommen, wobei letztere mit ca. 70 % des Risikos den Hauptanteil einnehmen....
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Background: In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report t...
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Background With a large array of disease modifying therapies (DMTs) for relapsing-remitting MS (RRMS), identifying the optimal treatment option for the individual patient is challenging and switching of immunotherapies is often required. The objective of this study was to systematically investigate reasons for DMT switching in patients on immunothe...
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Background: Gait deficits are common in multiple sclerosis (MS) and contribute to disability but may not be easily detected in the early stages of the disease. Objectives: We investigated whether sensor-based gait analysis is able to detect gait impairments in patients with MS (PwMS). Methods: A foot-worn sensor-based gait analysis system was...
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Introduction Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and re...