Klaus Fassbender

Universität des Saarlandes, Saarbrücken, Saarland, Germany

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Publications (198)849.35 Total impact

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    ABSTRACT: Aims: Status epilepticus and seizure clusters are common neurological emergencies. The purpose of this monocentric, retrospective cohort study was to comparatively assess different antiepileptic approaches in the treatment of status epilepticus and seizure clusters, which were nonresponsive to benzodiazepines. Methods: We reviewed medical records of 66 patients, who were treated for status epilepticus or seizure clusters in the Department of Neurology at the University of the Saarland between January 2007 and July 2012, and failed to respond to benzodiazepines with the equivalent dosage of at least 20 mg of diazepam. As endpoints, we analyzed both the effectiveness of lacosamide, levetiracetam, valproic acid, and phenytoin used as second- and third-line therapy, and the Glasgow Outcome Scale at day 7. Results: Sixty-one (92.4%) of the patients had status epilepticus, and 5 (7.6%) had seizure clusters. The compared drugs were equally effective in terminating seizures. There was also no significant difference in the Glasgow Outcome Scale (P = 0.60) after 7 days. Conclusion: Our data support the use of the modern antiepileptic treatment strategies, such as levetiracetam, valproic acid, and lacosamide in the treatment of status epilepticus and seizure clusters.
    No preview · Article · Feb 2016 · CNS Neuroscience & Therapeutics
  • I Keller · C Flöter · A Ragoschke-Schumm · K Faßbender
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    ABSTRACT: Background and objectives: When the National Socialists (NS) came to power in 1933, the German health care system was reorganized according to the principles of eugenics. Neuropsychiatric patients were victims of compulsory sterilisation and "euthanasia". As the Saar territory did not become part of the German Reich until the 1 March 1935, it is of special interest how quickly and completely NS health care policies were implemented. Methods: The analysis is based on medical records of the Homburg State Hospital's (HSH) clinic for nervous diseases from 1929 to 1945 (n =7,816) found in the Saarland University Medical Centre. Results: 1,452 patients were sterilised by force between 1935 and 1939 in the HSH. The most frequent diagnoses were congenital debility, schizophrenia, and epilepsy. Some of the 441 Homburg patients who were transferred to other mental hospitals from 1939 to 1940 were killed in the context of "Aktion T4" and presumably in a nonsystematic manner. Conclusions: NS health care policies were implemented immediately after incorporation of the Saar territory in 1935. Physicians of the HSH were involved directly in compulsory sterilisation of neuropsychiatric patients. An initial intention to kill by the time of patient transfers from Homburg cannot be proven. Further research concerning the killing centres is necessary.
    No preview · Article · Jan 2016 · Der Nervenarzt
  • S Walter · I Q Grunwald · K Fassbender
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    ABSTRACT: Clinical issue and diagnostic standards: The management of acute stroke patients suffers from several major problems in the daily clinical routine. In order to achieve optimal treatment a complex diagnostic work-up and rapid initiation of therapy are necessary; however, most patients arrive at hospital too late for any type of acute stroke treatment, although all forms of treatment are highly time-dependent according to the generally accepted "time is brain" concept. Diagnostic innovations: Recently, two randomized clinical trials demonstrated the feasibility of prehospital stroke diagnostic work-up and treatment. This was accomplished by use of a specialized ambulance, equipped with computed tomography for multimodal imaging and a point-of-care laboratory system. Performance: In both trials the results demonstrated a clear superiority of the prehospital treatment group with a significant reduction of treatment times, significantly increased number of patients treated within the first 60 min after symptom onset and an optimized triage to the correct target hospital. Achievements and practical recommendations: Currently, mobile stroke units are in operation in various countries and should lead to an improvement in stroke treatment; nevertheless, intensive research is still needed to analyze the best framework settings for prehospital stroke management.
    No preview · Article · Jan 2016 · Der Radiologe
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    ABSTRACT: Amyloid β (Aβ) damages neurons and triggers microglial inflammatory activation in the Alzheimer's disease (AD) brain. BACE1 is the primary enzyme in Aβ generation. Neuroinflammation potentially up-regulates BACE1 expression and increases Aβ production. In Alzheimer's amyloid precursor protein-transgenic mice and SH-SY5Y cell models, we specifically knocked out or knocked down gene expression of mapk14, which encodes p38α-MAPK, a kinase sensitive to inflammatory and oxidative stimuli. Using immunological and biochemical methods, we observed that reduction of p38α-MAPK expression facilitated the lysosomal degradation of BACE1, decreased BACE1 protein and activity, and subsequently attenuated Aβ generation in the AD mouse brain. Inhibition of p38α-MAPK also enhanced autophagy. Blocking autophagy by treating cells with 3-methyladenine or overexpressing dominant-negative ATG5 abolished the deficiency of p38α-MAPK-induced BACE1 protein reduction in cultured cells. Thus, our study demonstrates that p38α-MAPK plays a critical role in the regulation of BACE1 degradation and Aβ generation in AD pathogenesis.
    Full-text · Article · Dec 2015 · Journal of Biological Chemistry
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    ABSTRACT: Background: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. Methods: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. Results: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item 'General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items 'Role limitation emotional' (p = 0.0007) and 'Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). Conclusions: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.
    No preview · Article · Oct 2015 · Cerebrovascular Diseases
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    ABSTRACT: Background: For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment ('time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. Methods: Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site ('stroke room'). Result: After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. Conclusion: This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location ('stroke room') saves crucial time until IAT.
    No preview · Article · Oct 2015 · Cerebrovascular Diseases
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    ABSTRACT: The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations.
    Full-text · Article · Sep 2015 · Zeitschrift für Gerontologie + Geriatrie
  • Ramona Halmer · Laura Davies · Yang Liu · Klaus Fassbender · Silke Walter
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    ABSTRACT: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis. © 2015 The Author(s) Published by S. Karger AG, Basel.
    No preview · Article · Aug 2015 · Cellular Physiology and Biochemistry
  • J. Bürmann · A. Devlioti · M. Manitz · P. Bialas · K. Faßbender · U. Dillmann

    No preview · Article · Aug 2015
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    ABSTRACT: A massive expansion of a GGGGCC repeat upstream of the C9orf72 coding region is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. Despite its intronic localization and lack of a canonical start codon, both strands are translated into aggregating dipeptide repeat (DPR) proteins: poly-GA, poly-GP, poly-GR, poly-PR and poly-PA. To address conflicting findings on the predominant toxicity of the different DPR species in model systems, we compared the expression pattern of the DPR proteins in rat primary neurons and postmortem brain and spinal cord of C9orf72 mutation patients. Only poly-GA overexpression closely mimicked the p62-positive neuronal cytoplasmic inclusions commonly observed for all DPR proteins in patients. In contrast, overexpressed poly-GR and poly-PR formed nucleolar p62-negative inclusions. In patients, most of the less common neuronal intranuclear DPR inclusions were para-nucleolar and p62 positive. Neuronal nucleoli in C9orf72 cases showed normal size and morphology regardless of the presence of poly-GR and poly-PR inclusions arguing against widespread nucleolar stress, reported in cellular models. Colocalization of para-nucleolar DPR inclusions with heterochromatin and a marker of transcriptional repression (H3K9me2) indicates a link to gene transcription. In contrast, we detected numerous intranuclear DPR inclusions not associated with nucleolar structures in ependymal and subependymal cells. In patients, neuronal inclusions of poly-GR, poly-GP and the poly-GA interacting protein Unc119 were less abundant than poly-GA inclusions, but showed similar regional and subcellular distribution. Regardless of neurodegeneration, all inclusions were most abundant in neocortex, hippocampus and thalamus, with few inclusions in brain stem and spinal cord. In the granular cell layer of the cerebellum, poly-GA and Unc119 inclusions were significantly more abundant in cases with FTLD than in cases with MND and FTLD/MND. Poly-PR inclusions were rare throughout the brain but significantly more abundant in the CA3/4 region of FTLD cases than in MND cases. Thus, although DPR distribution is not correlated with neurodegeneration spatially, it correlates with neuropathological subtypes.
    Full-text · Article · Jun 2015 · Acta Neuropathologica
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    ABSTRACT: Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with antidepressants. Although these drugs have been used for many years, their exact mode of action is still unknown. It has been suggested that many antidepressants act by increasing the concentrations of serotonergic transmitters in the synaptic space. However, recent studies have examined the effects of antidepressants on neurogenesis in the hippocampus, the restoration of hippocampal neuronal networks that may be affected by major depression, and the regulation of the hypothalamic-pituitary-adrenal axis by immature neurons in the hippocampus. Here we present and discuss a novel hypothesis suggesting that these events are regulated by the concentrations of sphingolipids, in particular ceramide, in the hippocampus. These concepts suggest that the acid sphingomyelinase/ceramide system plays a central role in the pathogenesis of major depression and may be a novel target for antidepressants. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Apr 2015 · Journal of Neurochemistry
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    ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular deposits of amyloid β peptide (Aβ) and microglia-dominated neuroinflammation. The therapeutic options for AD are currently limited. In this study, we investigated the antiinflammatory effects and the underlying molecular mechanisms of Ginkgo biloba extract EGb 761 when administered to TgCRND8 AD mice, which overexpress human Alzheimer's amyloid precursor protein (APP) specifically in neurons. We gave APP-transgenic mice EGb 761 as a dietary supplement for 2 or 5months. Plasma concentrations of EGb 761 components in mice were in the same range as such concentrations in humans taking EGb 761 at the recommended dose (240mg daily). Treatment with EGb 761 for 5months significantly improved the cognitive function of the mice as measured by the Barnes Maze test. It also attenuated the loss of synaptic structure proteins, such as PSD-95, Munc18-1, and SNAP25. Treatment with EGb 761 for 5months inhibited microglial inflammatory activation in the brain. The effects of treatment with EGb 761 for 2months were weak and not statistically significant. Moreover, EGb 761 activated autophagy in microglia. Treatment with EGb 761 decreased Aβ-induced microglial secretion of TNF-α and IL-1β and activation of caspase-1, both of which were abolished by the inhibition of autophagy. Treatment with EGb 761 also reduced the concentrations of NLRP3 protein that colocalized with LC3-positive autophagosomes or autolysosomes in microglia. Additionally, long-term treatment with EGb 761 may reduce cerebral Aβ pathology by inhibiting β-secretase activity and Aβ aggregation. Therefore, long-term treatment with G.biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology by antiinflammatory and Aβ-directed mechanisms. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jan 2015 · Brain Behavior and Immunity
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    ABSTRACT: Background: Recently, a strategy for treating stroke directly at the emergency site was developed. It was based on the use of an ambulance equipped with a scanner, a point-of-care laboratory, and telemedicine capabilities (Mobile Stroke Unit). Despite demonstrating a marked reduction in the delay to thrombolysis, this strategy is criticized because of potentially unacceptable costs. Methods: We related the incremental direct costs of prehospital stroke treatment based on data of the first trial on this concept to one year direct cost savings taken from published research results. Key parameters were configuration of emergency medical service personnel, operating distance, and population density. Model parameters were varied to cover 5 different relevant emergency medical service scenarios. Additionally, the effects of operating distance and population density on benefit-cost ratios were analyzed. Results: Benefits of the concept of prehospital stroke treatment outweighed its costs with a benefit-cost ratio of 1.96 in the baseline experimental setting. The benefit-cost ratio markedly increased with the reduction of the staff and with higher population density. Maximum benefit-cost ratios between 2.16 and 6.85 were identified at optimum operating distances in a range between 43.01 and 64.88 km (26.88 and 40.55 miles). Our model implies that in different scenarios the Mobile Stroke Unit strategy is cost-efficient starting from an operating distance of 15.98 km (9.99 miles) or from a population density of 79 inhabitants per km2 (202 inhabitants per square mile). Conclusion: This study indicates that based on a one-year benefit-cost analysis that prehospital treatment of acute stroke is highly cost-effective across a wide range of possible scenarios. It is the highest when the staff size of the Mobile Stroke Unit can be reduced, for example, by the use of telemedical support from hospital experts. Although efficiency is positively related to population density, benefit-cost ratios can be greater than 1 even in rural settings.
    Full-text · Article · Dec 2014 · Cerebrovascular Diseases
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    ABSTRACT: There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline. After 5 years, eight persons (1.0 %) were diagnosed with Parkinson’s Disease (PD). Of those, seven (87.5 %) had motor worsening ≥3 points on the UPDRS-III from baseline to follow-up, one had two points increase. Of the 788 people without PD, 568 (72.1 %) showed no increase in the UPDRS-III scale, 220 (27.9 %) had ≥1 point increase and out of these 104 (13.2 %) had an increase of ≥3 points in the UPDRS-III score after 5 years. We identified an age >60 years (relative risk, RR = 1.7; confidence interval, CI 1.3–2.1) and the occurrence of ≥2 risk factors (RR = 1.5; CI 1.2-1.9) as possible predictors of motor progression. After 5 years, individuals with an increase in the UPDRS-III score had more often a one-sided reduced arm swing (p p UPDRS-III parallels the development of prodromal markers for neurodegenerative diseases in the elderly population.
    No preview · Article · Dec 2014 · Journal of Neurology
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    K Fassbender · L Frölich
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    ABSTRACT: This article presents the evidence-based pharmacotherapeutic options for the most common forms of neurodegenerative dementia. The aim is to present the recommendations derived from the relevant studies on the neurological, psychiatric and geriatric practice of treatment for dementia patients. The text is derived from the 2009 guidelines of the German Society of Neurology (DGN, lead management: K. Fassbinder), the S3 guidelines of the DGN/German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN, lead management: G. Deuschl and W. Maier) and the latest amendments of the European Federation of Neurological Societies/European Society of Neurology (EFNS-ENS, Sorbi et al. Eur J Neurol 19:1159-1179, 2012) guidelines. The forms of neurodegenerative dementia addressed are Alzheimer's disease, frontotemporal dementia and Lewy body dementia. Specific statements on the treatment of dementia in Parkinson's disease and vascular dementia can be found in separate guidelines. An analogous article on psychosocial interventions was recently published in Der Nervenarzt (Kurz, Nervenarzt 84:93-103, 2013).
    Full-text · Article · Dec 2014 · Der Nervenarzt
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    ABSTRACT: Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Aβ clearance. However, studies examining innate immunity in Aβ pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKβ, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKβ in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Aβ load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKβ deficiency enhanced microglial recruitment to Aβ deposits and facilitated Aβ internalization, perhaps by inhibiting TGF-β-SMAD2/3 signaling, but did not affect Aβ production and efflux. Therefore, inhibition of IKKβ signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Aβ clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression.
    Preview · Article · Sep 2014 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    ABSTRACT: We investigated in vivo brain nicotinic acetylcholine receptor (nAChR) distribution in cognitively intact subjects with Parkinson's disease (PD) at an early stage of the disease. Fourteen patients and 13 healthy subjects were imaged with single photon emission computed tomography and the radiotracer 5-[(123)I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine ([(123)I]5IA). Patients were selected according to several criteria, including short duration of motor signs (<7 years) and normal scores at an extensive neuropsychological evaluation. In PD patients, nAChR density was significantly higher in the putamen, the insular cortex and the supplementary motor area and lower in the caudate nucleus, the orbitofrontal cortex, and the middle temporal gyrus. Disease duration positively correlated with nAChR density in the putamen ipsilateral (ρ = 0.56, p < 0.05) but not contralateral (ρ = 0.49, p = 0.07) to the clinically most affected hemibody. We observed, for the first time in vivo, higher nAChR density in brain regions of the motor and limbic basal ganglia circuits of subjects with PD. Our findings support the notion of an up-regulated cholinergic activity at the striatal and possibly cortical level in cognitively intact PD patients at an early stage of disease.
    Full-text · Article · Aug 2014 · Frontiers in Aging Neuroscience
  • Ramona Halmer · Silke Walter · Klaus Faßbender
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    ABSTRACT: Multiple Sclerosis (MS) is the most common cause for permanent disability in young adults. Current pathophysiological understanding has identified an autoaggressive immune reaction with infiltration of immune cells into the central nervous system and local inflammatory and demyelinating reactions. The current therapy focuses on a modulation or suppression of immune functions. Sphingolipids, main components of nervous tissue, have been linked to MS already 60 years ago with the description of an unusual myelin lipid distribution in diseased patients. There is tremendous information developing on the role of different sphingolipids in MS. Antibodies against sphingomyelin, sulfatide or galacosylceramide have been detected in serum or CSF of MS patients, although up to now, this knowledge did not find its way into clinical use. Ceramide and the enzymes linked to its production have been described to play a pivotal role in oligendrocyte damage and demyelination. Nowadays, especially sphingosine-1-phosphate (S1P) is in the focus of pathophysiological research and therapy development. A S1P analogue, FTY720, is a widely distributed therapy against relapsing-remitting MS, attenuating the emigration of activated, autoreactive lymphocytes from lymph nodes, thereby preventing new inflammatory infiltration into the central nervous system. Beside, there is more and more evidence, that especially S1P receptors on oligodendrocytes and astrocytes are involved in demyelination processes and subsequent axonal degeneration, important features of chonic progressive MS disease course. Further information and research on the manifold role of sphingolipids are needed to prepare the ground for further clinical trials. This review focuses on the current knowledge of the role of sphingolipids in MS and describes the current therapeutical implications. © 2014 S. Karger AG, Basel.
    No preview · Article · Jun 2014 · Cellular Physiology and Biochemistry
  • E. Lyros · S. Walter · I. Keller · P. Papanagiotou · K. Fassbender
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    ABSTRACT: Introduction Capecitabine, a 5-fluorouracil (5FU) pro-drug, is increasingly used in breast and gastrointestinal cancers due to its more convenient oral route of administration when compared to 5FU. Despite its widespread use, there are only a few reports on capecitabine CNS toxicity, while the pathogenic basis of such toxicity remains unclear. Case A 69-year-old male presented with recurrent generalized seizures 2.5 months after preoperative chemoradiotherapy with capecitabine in locally advanced rectal cancer. Brain MRI revealed a diffuse, subcortical white matter alteration suggestive of vasogenic edema. The diagnosis of toxic encephalopathy was supported after elimination of alternative causes of the neurological dysfunction and complete resolution of clinical and imaging findings after 3 months of no further chemotherapy. Conclusions Given the expanding use of capecitabine, physicians should be aware of this potential complication when a neurological worsening occurs during or after treatment with this chemotherapeutic agent. In our case, as in previously described cases encephalopathy was characterized by a favorable course after cessation of the drug. Vasogenic edema rather than cytotoxic edema may play a pivotal pathogenetic role in this form of encephalopathy.
    No preview · Article · May 2014 · NeuroToxicology
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    ABSTRACT: The enteric nervous system (ENS) has to respond to continuously changing microenvironmental challenges within the gut and is therefore dependent on a neural stem cell niche to keep the ENS functional throughout life. In this study, we hypothesize that this stem cell niche is also affected during inflammation and therefore investigated lipopolysaccharides (LPS) effects on enteric neural stem/progenitor cells (NSPCs). NSPCs were derived from the ENS and cultured under the influence of different LPS concentrations. LPS effects upon proliferation and differentiation of enteric NSPC cultures were assessed using immunochemistry, flow cytometry, western blot, Multiplex ELISA and real-time PCR. LPS enhances the proliferation of enteric NSPCs in a dose-dependent manner. It delays and modifies the differentiation of these cells. The expression of the LPS receptor toll-like receptor 4 on NSPCs could be demonstrated. Moreover, LPS induces the secretion of several cytokines. Flow cytometry data gives evidence for individual subgroups within the NSPC population. ENS-derived NSPCs respond to LPS in maintaining at least partially their stem cell character. In the case of inflammatory disease or trauma where the liberation and exposure to LPS will be increased, the expansion of NSPCs could be a first step towards regeneration of the ENS. The reduced and altered differentiation, as well as the induction of cytokine signalling, demonstrates that the stem cell niche may take part in the LPS-transmitted inflammatory processes in a direct and defined way.
    Full-text · Article · Apr 2014 · Journal of Cellular and Molecular Medicine

Publication Stats

7k Citations
849.35 Total Impact Points

Institutions

  • 2006-2016
    • Universität des Saarlandes
      • Klinik für Neurologie
      Saarbrücken, Saarland, Germany
  • 2006-2013
    • Universitätsklinikum des Saarlandes
      Homburg, Saarland, Germany
  • 1994-2009
    • Universität Heidelberg
      • • Department of Neurology
      • • Institute of Clinical Chemistry
      Heidelburg, Baden-Württemberg, Germany
  • 1991-2009
    • Felix Platter Hospital
      Bâle, Basel-City, Switzerland
  • 2002-2005
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
  • 2001-2002
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 1992-1997
    • Max Planck Institute of Psychiatry
      München, Bavaria, Germany
  • 1992-1993
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland