Background: Despite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clinic since 2016. This study serves as… Read more »
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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis.
Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING). However, activation of neuronal STING requires its detachment from the stromal interaction molecule 1 (STIM1),… Read more »
Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) – A cluster- randomised controlled trial and mixed methods process evaluation.
Objective: To evaluate a nurse-led decision coaching programme aiming to redistribute health professionals‘ tasks to support immunotherapy decision-making in people with multiple sclerosis (MS). Methods: Cluster-randomised controlled trial with an accompanying mixed methods process evaluation (2014 – 2018). We planned to recruit 300 people with clinically isolated syndrome or relapsing-remitting MS facing immunotherapy decisions in… Read more »
Benefits of aHSCT over alemtuzumab in patients with multiple sclerosis besides disability and relapses: Sustained improvement in cognition and quality of life.
Background: Autologous hematopoietic stem cell transplantation (aHSCT) exhibits promising results for multiple sclerosis (MS) in the short term. We investigated the long-term outcome differences in disease progression and cognitive impairment after aHSCT and alemtuzumab treatment. Methods: 20 patients receiving aHSCT and 21 patients treated with alemtuzumab between 2007 and 2020 were included in this monocentric… Read more »
Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.
Background: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and… Read more »
G9a dictates neuronal vulnerability to inflammatory stress via transcriptional control of ferroptosis.
Neuroinflammation leads to neuronal stress responses that contribute to neuronal dysfunction and loss. However, treatments that stabilize neurons and prevent their destruction are still lacking. Here, we identify the histone methyltransferase G9a as a druggable epigenetic regulator of neuronal vulnerability to inflammation. In murine experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS), we found… Read more »
Development and evaluation of evidence-based patient information handbooks about multiple sclerosis immunotherapies.
Background: Multiple sclerosis treatment options are increasing. Evidence-based patient information (EBPI) are therefore crucial to enable patient involvement in decision making. Based on earlier work on decision support, patient information handbooks on 8 MS immunotherapies were developed, piloted and evaluated with support from the German Clinical Competence Network MS and the German MS Society. Methods:… Read more »
Managing neuropsychological impairment in multiple sclerosis – Controlled study on a standardized metacognitive intervention (MaTiMS)
Objective: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system of potential autoimmune origin that is frequently associated with neuropsychiatric symptoms and cognitive deficits, as well as with fatigue, stress and psychosocial burden. In the present controlled multi-centre trial we investigated whether two specific neuropsychological interventions (1. metacognitive training (MaTiMS);… Read more »
Implementation study of the 2021 German guideline for diagnosis and treatment of multiple sclerosis
Background: In May 2021, a new guideline on the diagnosis and treatment of multiple sclerosis and related disorders was released in Germany. Since the success of a guideline depends on how it integrates into everyday clinical practice, the German Society for Neurology (DGN) has launched a multimethod implementation project. Here we report on the results… Read more »
Arm Ergometry to Improve Mobility in Progressive Multiple Sclerosis (AMBOS)-Results of a Pilot Randomized Controlled Trial
Background: Walking disability is one of the most frequent and burdening symptoms of progressive multiple sclerosis (MS). Most of the exercise intervention studies that showed an improvement in mobility performance were conducted in low to moderately disabled relapsing-remitting MS patients with interventions using the legs. However, MS patients with substantial walking disability hardly can perform… Read more »
Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the… Read more »
Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis
MS is a chronic autoimmune disease of the CNS associated with serious physical and cognitive disability. MS manifests most commonly in young adults with a relapsingremitting disease course (RRMS), in which recurrent episodes (relapses) of neurological symptoms are followed by clinical remission. The majority of MS patients develop a progressive form of the disease, in… Read more »
Long-term prognostic counselling in people with multiple sclerosis using an online analytical processing tool.
Background: Prognostic counselling is a sensitive issue in medicine and especially so in MS due to the highly heterogeneous disease course. However, people with MS (pwMS) seek prognostic information. The web-based ‚Evidence-Based Decision Support Tool in Multiple Sclerosis‘ (EBDiMS) uses data of 717 patients from the London/Ontario cohort to calculate personalized long-term prognostic information. Objective:… Read more »
Possible determinants of long-term adherence to physical activity in multiple sclerosis-theory-based development of a comprehensive questionnaire and results from a German survey study.
Purpose: To examine the possible contributions of capability, opportunity, and motivation for explaining long-term physical activity among people with multiple sclerosis and to report the results of a German survey study.Methods: The questionnaire, which was based on an expert interview study and behavior change theory, was structured and detailed applying the Theoretical Domains Framework. A… Read more »
Bassoon proteinopathy drives neurodegeneration in multiple sclerosis.
Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression… Read more »
Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy… Read more »
Comprehension of confidence intervals – development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial
BACKGROUND: Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. METHODS: We developed… Read more »
Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation
Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activityregulated… Read more »
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) is permeable to Na+ and Ca2+, and excessive accumulation of these ions is associated with axonal degeneration. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After… Read more »
Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis.
The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4(+) T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8(+) T cells are controversial. We have generated humanized mice expressing the… Read more »
TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.
In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this… Read more »
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