The neuropathobiology of multiple sclerosis.

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Chronic low-grade inflammation and neuronal deregulation are two components of a smoldering disease activity that drives the progression of disability in people with multiple sclerosis (MS). Although several therapies exist to dampen the acute inflammation that drives MS relapses, therapeutic options to halt chronic disability progression are a major unmet clinical need. The development of… Read more »

„A second birthday“? Experiences of persons with multiple sclerosis treated with autologous hematopoietic stem cell transplantation-a qualitative interview study.

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Introduction and objective: Autologous hematopoietic stem cell transplantation (aHSCT) is a promising treatment option for persons with multiple sclerosis (pwMS). Patients undergoing aHSCT face unique challenges in all aspects of life. In this study, we explored the lived experiences of pwMS undergoing aHSCT. Methods: Semi-structured interviews of 12 pwMS treated with aHSCT were conducted using… Read more »

Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.

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Background: Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which… Read more »

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) – A cluster- randomised controlled trial and mixed methods process evaluation.

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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 »

Effectiveness of motivational interviewing on medication adherence for the prevention of recurrent stroke or transient ischemic attack: Systematic review of randomized controlled trials.

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Background and purpose: This systematic review examines the effectiveness of motivational interviewing (MI) on medication adherence for preventing recurrent stroke and transient ischemic attack (TIA). Methods: MEDLINE (via PubMed), CINAHL, PsycINFO, CENTRAL, and ClinicalTrials.gov were searched from inception to 12 June 2023. Randomized controlled trials comparing MI with usual care or interventions without MI in… Read more »

Astrocytic uptake of posttranslationally modified amyloid-β leads to endolysosomal system disruption and induction of pro-inflammatory signaling.

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The disruption of astrocytic catabolic processes contributes to the impairment of amyloid-β (Aβ) clearance, neuroinflammatory signaling, and the loss of synaptic contacts in late-onset Alzheimer’s disease (AD). While it is known that the posttranslational modifications of Aβ have significant implications on biophysical properties of the peptides, their consequences for clearance impairment are not well understood…. Read more »

Childhood and adolescence factors and multiple sclerosis: results from the German National Cohort (NAKO).

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Background: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. Methods: Data from the baseline assessment of… Read more »

Treatment of Cerebral Histiocytosis With Low Dose of Cobimetinib: A Report of 2 Cases.

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Objectives: Histiocytic disorders are pathologic expansions of myeloid cells in multiple organs, including the CNS. They share activation of the MAP kinase pathway due to either BRAFV600E variant or other variants in the RAS-RAF-MEK-ERK pathway. The rarity and heterogeneity of the disease only enable therapy through pathophysiologic considerations. Methods: We present 2 histiocytosis cases without… Read more »

CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis.

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Background: Progressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused by the proliferation of immune cells residing in the central nervous system (CNS), including B cells. Although inflammatory activity can be prevented by immunomodulatory therapies during early disease, such therapies typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell therapies… Read more »

Evaluating Relapse Knowledge in People with Multiple Sclerosis: A Cross-Sectional Study on the Development and Validation of the Relapse Knowledge Questionnaire.

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„Background: Multiple sclerosis (MS) knowledge is a prerequisite for active patient engagement in medical decision-making. Treatment of relapses in MS is a clinical field with many uncertainties and each acute relapse requires decisions regarding possible options for action, indicating the need for patient involvement. However, there is no validated instrument assessing relapse knowledge in people… Read more »

14-3-3 ζ/δ-reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2.

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„Introduction: Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes synaptic cleavage before tau aggregation appears. Methods: We investigated 104 participants across the… Read more »

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit.

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Background: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. Methods: We retrospectively analyzed data collected during a single-center observational study (March… Read more »

Sotrovimab in Hospitalized Patients with SARS-CoV-2 Omicron Variant Infection: a Propensity Score-Matched Retrospective Cohort Study.

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In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June… Read more »

History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.

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Background and purpose: This study aimed to investigate if pre-existing neurological conditions, such as dementia and a history of cerebrovascular disease, increase the risk of severe outcomes including death, intensive care unit (ICU) admission and vascular events in patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2022, when Omicron was the… Read more »

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

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“ Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease… Read more »

Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies.

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Objectives: Neurodegeneration is considered a relevant pathophysiologic feature in neurologic disorders associated with antibodies against glutamic acid decarboxylase 65 (GAD65). In this study, we investigate surrogates of neuroaxonal damage in relation to disease duration and clinical presentation. Methods: In a multicentric cohort of 50 patients, we measured serum neurofilament light chain (sNfL) in relation to… Read more »

Comparative analysis of characteristics and outcomes in hospitalized COVID-19 patients infected with different SARS-CoV-2 variants between January 2020 and April 2022 – A retrospective single-center cohort study.

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Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the roll-out of vaccines and therapeutic agents, as well as the emergence of novel SARS-CoV-2 variants, have shown significant effects on disease severity. Methods: Patients hospitalized at our center between January 2020 and April 2022 were attributed to subgroups depending on which SARS-CoV-2 variant… Read more »

Endothelial Indoleamine-2,3-Dioxygenase-1 is not Critically Involved in Regulating Antitumor Immunity in the Central Nervous System.

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The vascular niche of malignant gliomas is a key compartment that shapes the immunosuppressive brain tumor microenvironment (TME). The blood-brain-barrier (BBB) consisting of specialized endothelial cells (ECs) and perivascular cells forms a tight anatomical and functional barrier critically controlling transmigration and effector function of immune cells. During neuroinflammation and tumor progression, the metabolism of the… Read more »

Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology.

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Background: Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181,… Read more »

Benefits of aHSCT over alemtuzumab in patients with multiple sclerosis besides disability and relapses: Sustained improvement in cognition and quality of life.

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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 »

Time to disability milestones and annualized relapse rates in NMOSD and MOGAD.

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Objective: To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age. Methods: We analyzed data from individuals with NMOSD and MOGAD… Read more »

A2A adenosine receptor-driven cAMP signaling in olfactory bulb astrocytes is unaffected in experimental autoimmune encephalomyelitis.

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„Introduction: The cyclic nucleotide cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger, which is known to play an important anti-inflammatory role. Astrocytes in the central nervous system (CNS) can modulate inflammation but little is known about the significance of cAMP in their function. Methods: We investigated cAMP dynamics in mouse olfactory bulb astrocytes in… Read more »

Body mass,neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis.

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Overweight and obesity can worsen disease activity in multiple sclerosis (MS). Although psychobiological stress processing is increasingly recognized as important obesity factor that is tightly connected to proinflammatory metabolic hormones and cytokines, its role for MS obesity remains unexplored. Consequently, we investigated the interplay between body mass index (BMI), neural stress processing (functional connectivity, FC),… Read more »

MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.

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Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA-mRNA network of inflamed motor neurons by leveraging cell type-specific miRNA and mRNA sequencing of… Read more »

Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease.

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Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals… Read more »

Plasma pTau-217 and N-terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid-β positive individuals.

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„Introduction: We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers. Methods: In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18 F]AZD4694 and tau-PET with [18 F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231,… Read more »

Mobile health interventions in multiple sclerosis: A systematic review.

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Background: Persons with multiple sclerosis (pwMS) might be particularly well suited to benefit from digital health applications because they are, on average, younger and less severely disabled than patients with many other chronic diseases. Many digital health applications for pwMS have been developed. Objectives: Analysis of the evidence of digital health applications to improve health… Read more »

Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline.

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„Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and… Read more »

The MoXFo initiative – study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis.

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„Background: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. Objectives: This paper outlines the work of the ‚Study design and methodology‘ group of the MoXFo (moving exercise research forward)… Read more »

The MoxFo initiative-Mechanisms of action: Biomarkers in multiple sclerosis exercise studies.

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Background: As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established. Objective: Establish recommendations for future mechanistic exercise studies in MS. Methods: In regular meetings, members of the mechanisms of action… Read more »

The MoXFo initiative – adherence: Exercise adherence, compliance and sustainability among people with multiple sclerosis: An overview and roadmap for research.

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We know very little about exercise adherence, compliance and sustainability in multiple sclerosis (MS), yet adherence is seemingly important for yielding immediate and sustained health benefits. This paper is focused on exercise adherence, compliance and sustainability in the context of informing research and practice involving MS. This focus is critical for clarifying terminology for future… Read more »

Acceptability of digital health application to empower persons with multiple sclerosis with moderate to severe disability: single-arm prospective pilot study.

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Background: Many persons with multiple sclerosis (pwMS) desire to learn how health behaviour changes (e.g., dietary adjustments, physical activity, improvements in stress management) might help them manage their disease. Previous research has shown that certain health behaviour changes can improve quality of life (QoL), fatigue and other MS outcomes. Digital health applications may be well… Read more »

„Activity Matters was great – I now realize: if I move, I’m fitter.“: development and process evaluation of a web-based program for persons with multiple sclerosis.

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„Purpose: Research shows that persons with mild to moderate multiple sclerosis are less physically active than healthy controls even though they would benefit from it. This study focusses on the feasibility testing and process evaluation of the pilot study of Activity Matters, a twelve-week web-based program, from Ireland, to increase physical activity in this population…. Read more »

Pathogeneric mechanisms and treatment targets in cerebral malaria.

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Malaria, the most prevalent mosquito-borne infectious disease worldwide, has accompanied humanity for millennia and remains an important public health issue despite advances in its prevention and treatment. Most infections are asymptomatic, but a small percentage of individuals with a heavy parasite burden develop severe malaria, a group of clinical syndromes attributable to organ dysfunction. Cerebral… Read more »

Health behaviors of people with multiple sclerosis and its associations with MS related outcomes: a German clinical cohort.

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Background: Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes. Objective: The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical… Read more »

Association of health behaviour and clinical manifestation in early multiple sclerosis in Germany – Baseline characteristics of the POWER@MS1 randomised controlled trial.

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Background: Receiving a multiple sclerosis (MS) diagnosis is a significant stressor. Therefore, highly individualised counselling is needed, especially in early MS. Modifiable risk factors (e.g. smoking and obesity) are gaining relevance in MS. Despite evidence for worse MS-related health outcomes, prevalence of adverse health behaviours, such as smoking and physical inactivity, is high across all… Read more »

Translation and validation of the multiple sclerosis walking scale 12 for the German population – the MSWS-12/D.

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Background: Gait impairment is a relevant problem in persons with multiple sclerosis (pwMS). The Multiple Sclerosis Walking Scale 12 (MSWS-12) is a valid Patient Reported Outcome Measure (PROM) to evaluate walking ability in pwMS. The aim of this study was to provide a linguistically valid translation of MSWS-12 into German language (MSWS-12/D) and to evaluate… Read more »

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

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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 »

Non-pharmacological randomized intervention trial for the management of neuropsychological symptoms in outpatients with progressive multiple sclerosis

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Purpose: Despite typically more pronounced cognitive and mental health issues in progressive disease courses of multiple sclerosis (PMS), rehabilitation research in this subgroup is rare. The efficacy of two non-pharmacological interventions with positive results from prior investigations was therefore examined in PMS specifically. Methods: Persons with PMS (pwPMS) received either computerized cognitive training (BrainStim), standardized… Read more »

Supporting brain health in multiple sclerosis: exploring the potential of neuroeducation combined with practical mindfulness exercises in the management of neuropsychological symptoms

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Objective: We aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit. Methods: Both interventions were administered… Read more »

Calcium Channel ß3 subunit regulates ATP-dependent migration of dendritic cells.

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Migratory dendritic cells (migDCs) continuously patrol tissues and are activated by injury and inflammation. Extracellular adenosine triphosphate (ATP) is released by damaged cells or actively secreted during inflammation and increases migDC motility. However, the underlying molecular mechanisms by which ATP accelerates migDC migration is not understood. Here, we show that migDCs can be distinguished from… Read more »

Factors associated with depressive mood at the onset of multiple sclerosis – an analysis of 781 patients of the German NationMS cohort.

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Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce. Objectives: To assess an association of MS… Read more »

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack Therapy and long-term management.

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This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize… Read more »

Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Disease: An Umbrella Systematic Review and Meta-Analysis.

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Importance: Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent. Objective: To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis… Read more »

Vagus nerve inflammation contributes to dysautonomia in COVID-19.

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Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and… Read more »

Jacob-induced transcriptional inactivation of CREB promotes Aß-induced synapse loss in Alzheimer’s disease.

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Synaptic dysfunction caused by soluble β-amyloid peptide (Aβ) is a hallmark of early-stage Alzheimer’s disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP-responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking… Read more »

GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses.

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G-protein coupled receptors (GPCR) regulate 3′,5′-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Several GPCRs have been identified to be crucial for Teff and Treg function. However,… Read more »

Visual function resits early neurodegeneration in the visual system in primary progressive multiple sclerosis.

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Background: Neurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood. Methods: We assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNfL) levels in a prospective PPMS cohort and matched healthy… Read more »

Physical fitness moderates the association between brain network impairment and both motor function and cognition in progressive multiple sclerosis.

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Background: Neurodegeneration leads to continuous accumulation of disability in progressive Multiple Sclerosis (MS). Exercise is considered to counteract disease progression, but little is known on the interaction between fitness, brain networks and disability in MS. Objective: The aim of this study to explore functional and structural brain connectivity and the interaction between fitness and disability… Read more »

Knowledge and worries on motherhood choice in multiple sclerosis – a cross-sectional study on patient-reported outcome measures.

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Background: Since multiple sclerosis (MS) is often diagnosed in young women, pregnancy is a common topic for women with MS (wwMS). The study aimed to assess the measurement properties of two patient-reported outcome measures on motherhood choice in MS, and to explore the information and support needs of wwMS concerning motherhood.Methods: We conducted an anonymous… Read more »

Effect of geometric distortion correction on thickness and volume measurements of cortical parcellations in 3D T1w gradient echo sequences.

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More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into… Read more »

Absence of self-reported neuropsychiatric and somatic symptoms after Omicron variant SARS-CoV-2 breakthrough infections.

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Persistent somatic and neuropsychiatric symptoms have been frequently described in patients after infection with severe acute respiratory syndrome coronavirus 2 even after a benign clinical course of the acute infection during the early phases of the coronavirus severe acute respiratory syndrome coronavirus 2 pandemic and are part of Long COVID. The Omicron variant emerged in… Read more »

Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis

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The term ’neuromyelitis optica spectrum disorders‘ (NMOSD) is used as an umbrella term that refers to aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica (NMO) and its formes frustes and to a number of closely related clinical syndromes without AQP4-IgG. NMOSD were originally considered subvariants of multiple sclerosis (MS) but are now widely recognized as disorders in… Read more »

Associations between individual depressive symptoms and immunometabolic characteristics in major depression.

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Inflammation and metabolic dysregulations are likely to underlie atypical, energy-related depressive symptoms such as appetite and sleep alterations. Indeed, increased appetite was previously identified as a core symptom of an immunometabolic subtype of depression. The aim of this study was 1) to replicate the associations between individual depressive symptoms and immunometabolic markers, 2) to extend… Read more »

Treatment of autoimmunity: The impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders.

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More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into… Read more »

The Psychological Impact of Parental Multiple Sclerosis on Childred and Adolescents: A Systematic Review.

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Background: Multiple sclerosis (MS) is a common debilitating neurologic disease that affects mostly young women. This review provides an overview of research on the psychosocial impact of parental MS on children to inform clinicians and support people with MS considering parenthood. Methods: A systematic review of the literature was performed by searching the MEDLINE, PsycINFO,… Read more »

Case report: JAK inhibition as promising treatment option of fatal RVCLS due to TREX1 mutation (pVAL235Glyfs*6).

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Introduction: Autosomal dominant mutations in the C-terminal part of TREX1 (pVAL235Glyfs*6) result in fatal retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) without any treatment options. Here, we report on a treatment of a RVCLS patient with anti-retroviral drugs and the janus kinase (JAK) inhibitor ruxolitinib. Methods: We collected clinical data of an extended… Read more »

Postpartum relapse risk in multiple sclerosis: a systematic review and meta-anlysis.

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The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine… Read more »

Cognition in patients with neuromyelitis optica spectrum disorders: A prospective multicentre study of 217 patients (CogniNMO-Study).

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Background: There is limited and inconsistent information on the prevalence of cognitive impairment in neuromyelitis optica spectrum disorders (NMOSD). Objective: To assess cognitive performance and changes over time in NMOSD. Methods: This study included data from 217 aquaporin-4-IgG-seropositive (80%) and double-seronegative NMOSD patients. Cognitive functions measured by Symbol Digit Modalities Test (SDMT), Paced Auditory Serial-Addition… Read more »

Development and evaluation of a website with patients experiences of multiple sclerosis: a mixed methods study.

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Background: A variety of management options (e.g., disease-modifying therapy, lifestyle interventions, rehabilitation) are available for persons with relapsing-remitting multiple sclerosis (MS). Besides coping with the diagnosis, persons with MS have to make complex decisions, e.g., regarding disease-modifying therapies. In addition to factual information, reports of patient experiences may support other patients in their decision-making. Therefore,… Read more »

Experiences of persons with multiple sclerosis with rehabilitation: A qualitative study interview.

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Background: Managing multiple sclerosis (MS) includes different treatment approaches. Rehabilitation is a key strategy in MS for improving functioning, activity and participation. As part of a larger study on overall patient experiences with different treatment approaches, this study aims to give an overview of different patients‘ experiences and perspectives on inpatient rehabilitation in MS. Methods:… Read more »

Experiences of persons with Multiple Sclerosis with lifestyle adjustment: A qualitative interview study.

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Background: Persons with Multiple Sclerosis (pwMS) follow individual strategies to cope with this highly heterogeneous disease. As surveys show, lifestyle habits play an important role in pwMS. However, little is known about individual experiences of pwMS with different lifestyle adjustment strategies.Objective: This study aims to describe and understand individual experiences of pwMS with lifestyle adjustments…. Read more »

Personality and its association with self-management in multiple sclerosis.

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Background: In a healthcare system which aims to empower the patient, self-management becomes increasingly important. In Multiple Sclerosis, an effective self-management is associated with various favorable health-related outcomes like improvement in quality of life, the reduction of depression and anxiety symptoms, and reduced healthcare costs. This study investigates the association between the Big Five personality… Read more »

Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination.

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Multiple sclerosis (MS) is a progressive inflammatory-demyelinating disease of the central nervous system. Increasing evidence suggests that vulnerable neurons in MS exhibit fatal metabolic exhaustion over time, a phenomenon hypothesized to be caused by chronic hyperexcitability. Axonal Kv7 (outward rectifying) and oligodendroglial Kir4.1 (inward rectifying) potassium channels have important roles in regulating neuronal excitability at… Read more »

Effects of the COVID-19 Pandemic on Patients with NMO Spectrum Disorders and MOG-Antibody-Associated Diseases: COPANMO(G)-Study.

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Background and objectives: To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). Methods: This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers… Read more »

CXCR5+PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation

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Gastrointestinal infections are a major cause for serious clinical complications in infants. The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++ CD4+ T cells (TFH cells). We investigated the ontogeny of CXCR5+PD-1++ CD4+ T cells in human intestines. While CXCR5+PD-1++ CD4+ T cells were absent in… Read more »

Driving ability and predictors for driving performance in Multiple Sclerosis: A systematic review.

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Objective: To provide an overview of the evidence on driving ability in persons with multiple sclerosis (PwMS), specifically to (i) study the impact of MS impairment on driving ability and (ii) evaluate predictors for driving performance in MS. Methods: To identify relevant studies, different electronic databases were screened in accordance with PRISMA guidelines; this includes… Read more »

Association of obesity with disease outcome in multiple sclerosis.

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Background: Obesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation. Methods: This nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were… Read more »

Topological reorganization of brain network might contribute to the resilience of cognitive functioning in mildly disabled relapsing remitting multiple sclerosis.

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Multiple sclerosis (MS) is an inflammatory and demyelinating disease which leads to impairment in several functional systems including cognition. Alteration of brain networks is linked to disability and its progression. However, results are mostly cross-sectional and yet contradictory as putative adaptive and maladaptive mechanisms were found. Here, we aimed to explore longitudinal reorganization of brain… Read more »

An interacitive web-based programme on relapse management for people with multiple sclerosis (POWER@MS2) – development, feasibility, and pilot testing of a complex intervention.

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Introduction: Despite the lack of high-quality evidence regarding its long-term effectiveness, intravenous corticosteroid therapy is recommended as the standard treatment of acute multiple sclerosis relapses in Germany. High financial expenses and the equivalent effectiveness of oral corticosteroid therapy contrast with this trend. There is an urgent need to provide patients with evidence-based and comprehensible information… Read more »

Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes.

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Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with… Read more »

The manifestation of affective symptoms in multiple sclerosis and discussion of the currently available diagnostic assessment tools.

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Introduction: In addition to physical and cognitive symptoms, patients with multiple sclerosis (MS) have an increased risk of experiencing mental health problems. Methods: This narrative review provides an overview of the appearance and epidemiology of affective symptoms in MS such as depression, anxiety, bipolar disorder, euphoria, and pseudobulbar affect. Furthermore, the association between affective symptoms… Read more »

Do Impulse Control Disorders Impair Car Driving Performance in Patients with Parkinson’s Disease?

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Background: Based on data regarding the prevalence of Parkinson’s disease (PD), the prevalence of impulsive control disorders (ICD) in PD, and the percentage of PD patients driving a car, it has to be assumed that at least 50,000 PD patients with ICD in Germany actively drive a car. However, these patients might be at risk… Read more »

Brestfeeding and risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

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Introduction: The causes of multiple sclerosis (MS) are not fully understood, yet. Genetic predisposition, environmental and lifestyle factors as well as an interplay thereof constitute relevant factors in the development of MS. Especially early-life risk factors such as having been breastfed may also be of relevance. Breast milk provides the new-born not only with essential… Read more »

„That would have been the perfect thing after diagnosis“: development of a digital lifestyle management application in multiple sclerosis.

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Background: A multiple sclerosis (MS) diagnosis urges decision-making on immunotherapies, while persons with MS (PwMS) need to develop a coping concept in parallel. At this stage, PwMS ask how they themselves may contribute to controlling the disease. Evidence suggests that maintaining a healthy lifestyle (e.g. physical activity and stress management) is a key factor for… Read more »

Validation of the German eHealth impact questionnaire for online health information users affected by multiple sclerosis.

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Background: Persons with multiple sclerosis (MS) are confronted by an overwhelming amount of online health information, which can be valuable but also vary in quality and aim. Therefore, it is of great importance for developers and providers of eHealth information to understand its impact on the users. The eHealth Impact Questionnaire (eHIQ) has been developed… Read more »

On model-based time trend adjustments in platform trials with non-concurrent controls.

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Background: Platform trials can evaluate the efficacy of several experimental treatments compared to a control. The number of experimental treatments is not fixed, as arms may be added or removed as the trial progresses. Platform trials are more efficient than independent parallel group trials because of using shared control groups. However, for a treatment entering… Read more »

Sarcoidosis as prime example of a granulomatous disease.

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Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the… Read more »

A glibenclamide-sensitive TRPM4-mediated component von CA1 excitatory postsynaptic potentials appears in experimental autoimmune encephalomyelitis.

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The transient receptor potential melastatin 4 (TRPM4) channel contributes to disease severity in the murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and to neuronal cell death in models of excitotoxicity and traumatic brain injury. As TRPM4 is activated by intracellular calcium and conducts monovalent cations, we hypothesized that TRPM4 may contribute to and… Read more »

G9a dictates neuronal vulnerability to inflammatory stress via transcriptional control of ferroptosis.

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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 »

The 27-Item Multiple Sclerosis Quality of Life Questionnaire: A New Brief Measure Including Treatment Burden and Work Life.

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Background: Treatment- and work-related aspects have been neglected in health-related quality of life (HRQOL) measures in multiple sclerosis (MS). We aimed to develop a brief instrument covering all important impairment-, activity-, participation-, and treatment-related aspects for use in research and practice. Methods: The 27-item Multiple Sclerosis Quality of Life Questionnaire (MS-QLQ27) was developed using open… Read more »

Alterations of NK Cell Phenotype During Pregnancy in Multiple Sclerosis.

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In multiple sclerosis (MS), relapse rate is decreased by 70-80% in the third trimester of pregnancy. However, the underlying mechanisms driving this effect are poorly understood. Evidence suggests that CD56bright NK cell frequencies increase during pregnancy. Here, we analyze pregnancy-related NK cell shifts in a large longitudinal cohort of pregnant women with and without MS,… Read more »

Neuronal Adenosine A1 Receptor is Critical for Olfactory Function but Unable to Attenuate Olfactory Dysfunction in Neuroinflammation.

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Adenine nucleotides, such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), as well as the nucleoside adenosine are important modulators of neuronal function by engaging P1 and P2 purinergic receptors. In mitral cells, signaling of the G protein-coupled P1 receptor adenosine 1 receptor (A1R) affects the olfactory sensory pathway by regulating high voltage-activated calcium channels and… Read more »

Negative Associations of Stress and Anxiety Levels with Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus.

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Background: Depression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related… Read more »

Immunotherapy for people with clinically isolated syndrome or relapsing-remitting multiple sclerosis: treatment response by demographic, clinical, and biomarker subgroups (PROMISE) – a systematic review protocol.

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Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine… Read more »

Identification of early neurodegenerative pathways in progressive multiple sclerosis.

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Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular… Read more »

Cross-Country Adaptation of a Psychological Flexibility Measure: The Comprehensive Assessment of Acceptance and Commitment Therapy Processes.

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Purpose: The Comprehensive assessment of Acceptance and Commitment Therapy (ACT) processes (CompACT) is a 23-item self-report questionnaire assessing psychological flexibility, which is the overarching construct underpinning the ACT framework. We conducted a two-phase project to develop validated versions of the CompACT in three languages: phase 1-cross-cultural adaptation; and phase 2-psychometric validation of the questionnaire for… Read more »

The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) –Critical Review facing the 20 anniversary

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The SLCMSR was formed as an international Multiple Sclerosis Trials, Research and Resource Center to identify clinical MRI and other predictors of the course of multiple sclerosis (MS) based on a large database of natural history and clinical trial data. Using an elaborate validation concept several key findings were published, challenging established outcome parameters and… Read more »

The immunology of multiple sclerosis.

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Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings… Read more »

Motherhood choice in multiple sclerosis (MoMS) development and piloting of patient-reported outcome measures.

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Background: Multiple sclerosis (MS) particularly affects women between the age of 20 and 40. Therefore, pregnancy is often an important issue for women with MS (wwMS), but misunderstandings, misinformation, and uncertainties about MS and pregnancy are common. We developed and pilot-tested two questionnaires, one on knowledge (MCKQ), and one on attitudes, coping strategies and worries… Read more »

Association of depression and obesity with C-reactive protein in Germany: a large nationally representative study.

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Introduction: Depression and obesity often occur comorbidly, and once both are present, they further increase the risk of developing other medical comorbidities, likely due to the underlying chronic low-grade inflammation. We investigated to what extent depression and obesity are associated with levels of high-sensitivity C-reactive protein (hsCRP) in a nationally representative sample of the German… Read more »

German guideline for diagnosis and treatment of multiple sclerosis – a survey focusing neurologists in daily practise.

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We performed a web-based survey among German-speaking neurologists to evaluate the acceptance of the 2021 German guideline in the diagnosis and treatment of multiple sclerosis. Based on 327 replies in total, the current survey largely reproduced the findings of an earlier, smaller survey on the prefinal consultation version of the guideline and confirmed high acceptance… Read more »

Central stress processing, T-cell responsitivity to stress hormones and disease severity in multiple sclerosis.

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Epidemiological, clinical and neuroscientific studies support a link between psychobiological stress and multiple sclerosis. Neuroimaging suggests that blunted central stress processing goes along with higher multiple sclerosis severity, neuroendocrine studies suggest that blunted immune system sensitivity to stress hormones is linked to stronger neuroinflammation. Until now, however, no effort has been made to elucidate whether… Read more »

Understanding Magnetic Resonance Imaging in Multiple Sclerosis (UMIMS): Development and Piloting of an Online Education Program About Magnetic Resonance Imaging for People With Multiple Sclerosis.

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Background: People with multiple sclerosis (pwMS) lack sufficient magnetic resonance imaging (MRI) knowledge to truly participate in frequently occurring MRI-related therapy decisions. An evidence-based patient information (EBPI) about MRI is currently lacking. Objective: The aim of this study was to develop an evidence-based online education program about limitations and benefits of MRI for pwMS. Ultimately,… Read more »

Proposal for Post Hoc Quality Control in Instrumented Motion Analysis Using Markerless Motion Capture: Development and Usability Study.

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Background: Instrumented assessment of motor symptoms has emerged as a promising extension to the clinical assessment of several movement disorders. The use of mobile and inexpensive technologies such as some markerless motion capture technologies is especially promising for large-scale application but has not transitioned into clinical routine to date. A crucial step on this path… Read more »

Early-onset late-life depression: Association with body mass index, obesity, and treatment response

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Early-onset (EOD) and late-onset (LOD) late-life depression might differ in etiology, clinical features, and treatment response. While EOD is more frequently associated with a family history of affective disorders and personality aspects, LOD is thought to be more strongly driven by acquired cerebrovascular risk factors associated with vascular pathology, executive dysfunction, and poor treatment response…. Read more »

Development and evaluation of evidence-based patient information handbooks about multiple sclerosis immunotherapies.

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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 »

Risk communication in acute stroke patients – from qualitative data to a pilot randomised controlled trial.

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Objectives: The probability of recurring strokes in patients with atrial fibrillation is high. Within 1.8 years, 6.6 % of the patients suffered a new stroke. While effective secondary prevention options exist, low adherence challenges effective medical treatment. The aim of our study was to examine the risk understanding of acute stroke patients and to find… Read more »

Managing neuropsychological impairment in multiple sclerosis – Controlled study on a standardized metacognitive intervention (MaTiMS)

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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 »

Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function.

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Background: Extend and dynamic of neurodegeneration in progressive Multiple Sclerosis (MS) might be reflected by global and regional brain perfusion, an outcome at the intercept between structure and function. Here, we provide a first insight in the evolution of brain perfusion and its association with disability in primary progressive MS (PPMS) over several years. Methods:… Read more »

Costs and Health-Related Quality of Life in Patients with NMO Spectrum Disorders and MOG-Antibody-Associated Disease: CHANGE NOM Study.

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ObjectiveTo evaluate costs and health-related quality of life (HRQoL) of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD).MethodsIn this multicenter cross-sectional study, data on consumption of medical and non-medical resources and work ability were assessed via patient questionnaires. Costs were analyzed in EUR for 2018 from the societal perspective. HRQoL was… Read more »

The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.

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Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients‘ brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary… Read more »

Treating sarcoidosis-associated progressive multifocal leukoencephalopathy with infliximab.

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Although most of the progressive multifocal leukoencephalopathy cases in sarcoidosis patients are explained by the treatment with immunosuppressive drugs, it is also reported in treatment-naive sarcoidosis patients, which implies a general predisposition of sarcoidosis patients for progressive multifocal leukoencephalopathy. Indeed, it was shown that active sarcoidosis patients have increased regulatory T cell frequencies which could… Read more »

Subcortical volumes as early predictors of fatigue in multiple sclerosis.

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Objective: Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after four years by applying structural equation modeling (SEM). Methods: This multi-center cohort study included 601 treatment-naive… Read more »

T1 Relaxation Times in the Cortex and Thalamus Are Associated With Working Memory and Information Processing Speed in Patients with Multiple Sclerosis

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Background: Cortical and thalamic pathologies have been associated with cognitive impairment in patients with multiple sclerosis (MS). Objective: We aimed to quantify cortical and thalamic damage in patients with MS using a high-resolution T1 mapping technique and to evaluate the association of these changes with clinical and cognitive impairment. Methods: The study group consisted of… Read more »

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

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Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the… Read more »

Implementation study of the 2021 German guideline for diagnosis and treatment of multiple sclerosis

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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 »

Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis

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Health-related quality of life (HRQoL) is an essential complementary parameter in the assessment of disease burden and treatment outcome in multiple sclerosis (MS) and can be affected by neuropsychiatric symptoms, which in turn are sensitive to psychological stress. However, until now, the impact of neurobiological stress and relaxation on HRQoL in MS has not been… Read more »

Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study

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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 trial.Methods: This randomised, placebo-controlled, double-blind phase… Read more »

Immune signature of multiple sclerosis-associated depression.

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Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes… Read more »

Reduced mitochondrial respiration in T cells of patients with major depressive disorder

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Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC). Despite comparable BMI scores and… Read more »

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders

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Background and objectives: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).Methods: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n… Read more »

Upregulation of Phosphodiesterase 2A Augments T Cell Activation by Changing cGMP/cAMP Cross-Talk

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3′,5′-cyclic adenosine monophosphate (cAMP) is well-known for its diverse immunomodulatory properties, primarily inhibitory effects during T cell activation, proliferation, and production of pro-inflammatory cytokines. A decrease in cAMP levels, due to the hydrolyzing activity of phosphodiesterases (PDE), is favoring inflammatory responses. This can be prevented by selective PDE inhibitors, which makes PDEs important therapeutic targets… Read more »

CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis

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Background and objectives: CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation…. Read more »

Patients experiences with multiple sclerosis disease-modifying therapies in daily life – a qualitative interview study

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Background: Besides coping with a disease with many uncertainties, people with relapsing-remitting multiple sclerosis face complex decisions concerning disease-modifying therapies (DMTs). In an interview study, we aimed to assess patients‘ experiences with DMTs.Methods: Problem-centred interviews were conducted with 50 people with relapsing-remitting multiple sclerosis in Germany using maximum variation sampling and covering all licensed DMTs…. Read more »

Evaluation of an interactive web-based programme on relapse management for people with multiple sclerosis (POWER@MS2): study protocol for a process evaluation accompanying a randomised controlled trial

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Introduction: Process evaluations accompanying complex interventions examine the implementation process of the underlying intervention, identify mechanisms of impact and assess contextual factors. This paper presents the protocol for a process evaluation conducted alongside the randomised controlled trial POWER@MS2. The trial comprises the evaluation of a web-based complex intervention on relapse management in 188 people with… Read more »

Microstructural white matter abnormalities in hypothyroidism evaluation with diffusion tensor imaging tract-based spatial statistical analysis

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Purpose: Hypothyroidism is presented in a wide range from neuropsychiatric problems including depression, memory and cognitive disorders to poor motor coordination. Against the background of morphologic, functional and molecular changes on the white and grey matter of the brain, we aimed to investigate the effects of hypothyroidism on white matter (WM) integrity using tract-based spatial… Read more »

Identification of the factor XII contact activation site enables sensitive coagulation diagnostics

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Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential… Read more »

A meta-analysis comparing first-line immunosuppressants in neuromyelitis optica

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Objective: As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta-analysis compares the efficacy of first-line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still… Read more »

Intrathecal Antibody Production Against Epstein-Barr, Herpes Simplex, and Other Neurotropic Viruses in Autoimmune Encephalitis

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Background and objectives: Neurotropic viruses are suspected to play a role in the pathogenesis of autoimmune diseases of the CNS such as the association between the Epstein-Barr virus (EBV) and multiple sclerosis (MS). A group of autoimmune encephalitis (AE) is linked to antibodies against neuronal cell surface proteins. Because CNS infection with the herpes simplex… Read more »

Arm Ergometry to Improve Mobility in Progressive Multiple Sclerosis (AMBOS)-Results of a Pilot Randomized Controlled Trial

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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 »

Decision-making about corticosteroids in relapses of multiple sclerosis – development of a questionnaire based on the theory of planned behaviour

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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 »

The stress-axis in multiple sclerosis: Clinical, cellular, and molecular aspects.

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Altered activity of the hypothalamus-pituitary-adrenal (HPA) stress-axis has been implicated in the pathogenesis and progression of multiple sclerosis (MS) and linked to the development of specific symptoms and comorbidities such as mood disorders, fatigue, or cognitive dysfunction. Overall the HPA-axis is activated or hyperresponsive in MS, though a hyporesponsive HPA-axis has been observed in a… Read more »

Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19

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COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory and immunological parameters of 173 patients with mild… Read more »

Complement-associated loss of CA2 inhibitory synapses in the demyelinated hippocampus impairs memory

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The complement system is implicated in synapse loss in the MS hippocampus, but the functional consequences of synapse loss remain poorly understood. Here, in post-mortem MS hippocampi with demyelination we find that deposits of the complement component C1q are enriched in the CA2 subfield, are linked to loss of inhibitory synapses and are significantly higher… Read more »

Immunological substrates of depressive symptoms in patients with severe obesity: An exploratory study

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In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non-depressed patients with obesity and normal-weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ-9). Cell frequencies were correlated with depressive symptom scores and waist-to-hip… Read more »

Pain, Depression, and Quality of Life in Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study of 166 AQP4 Antibody-Seropositive Patients

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Objectives: To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort. Methods: We included 166 patients with aquaporin-4-seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief… Read more »

Activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) enhances dendritic cell vaccination in experimental melanoma

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Dendritic cell (DC) vaccination has proven to be an effective and safe adjuvant for cancer immunotherapies. As the presence of DCs within the tumor microenvironment promotes adaptive antitumor immunity, enhancement of DC migration toward the tumor microenvironment following DC vaccination might represent one possible approach to increase its therapeutic efficacy. While recent findings suggest the… Read more »

SnapShot: Neuronal dysfunction in inflammation

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Neuronal function relies on tightly controlled cytoskeleton transport with adaptive cargo trafficking as prerequisite for synaptic transmission. During inflammation in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), axonal transport efficiency declines, followed by neurodegeneration. Furthermore, neuroinflammation causes an imbalance between excitatory and inhibitory transmission, triggering synaptic dysfunction and loss. Recent data suggest that neuronal… Read more »

aHSCT is superior to alemtuzumab in maintaining NEDA and improving cognition in multiple sclerosis

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Objective: Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly recognized as a potential therapy for patients with highly active multiple sclerosis (MS). This study aims to assess outcome differences in disease activity in MS patients treated either with aHSCT or alemtuzumab. Methods: We conducted a monocentric registry-based cohort study by recording the clinical course (EDSS… Read more »

Association of Fatigue Severity With Maladaptive Coping in Multiple Sclerosis: A Data-Driven Psychodynamic Perspective

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Fatigue in persons with multiple sclerosis (PwMS) is severely disabling. However, the underlying mechanisms remain incompletely understood. Recent research suggests a link to early childhood adversities and psychological trait variables. In line with these studies, this paper took a psychodynamic perspective on MS-fatigue. It was hypothesized that fatigue could represent a manifestation of maladaptive coping… Read more »

Cognitive performance shows domain specific associations with regional cortical thickness in multiple sclerosis

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Multiple Sclerosis (MS) patients often suffer from significant cognitive impairment. Earlier research has shown relationships between regional cortical atrophy and cognitive deterioration. However, due to a large number of neuropsychological assessments and a heterogenous pattern of cognitive deficits in MS patients, reported associations patterns are also heterogenous. Using an extensive neuropsychological battery of 23 different… Read more »

Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis: A Randomized, Placebo-Controlled Trial

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Objective: To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up… Read more »

Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4+ T cells in primary sclerosing cholangitis

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Background and aims: Little is known on the composition of intrahepatic immune cells and their contribution to the pathogenesis of primary sclerosing cholangitis (PSC). We here aimed to create an atlas of intrahepatic T cells and thereby in detail characterize T cells in human inflamed liver. Methods: Different single-cell RNA sequencing methods were combined with… Read more »

Delayed access to conscious processing in multiple sclerosis: Reduced cortical activation and impaired structural connectivity

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Although multiple sclerosis (MS) is frequently accompanied by visuo-cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were… Read more »

Oculomotor Fatigue and Neuropsychological Assessments mirror Multiple Sclerosis Fatigue

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Fatigue is a major complaint in MS. Up to now no objective assessment tools have been established which hampers any treatment approach. Previous work has indicated an association of fatigue with cognitive measures of attention. Oculomotor tests have been established in healthy individuals as a read-out of fatigue, and to some extent in MS patients…. Read more »

How to measure fluctuating impairments in people with MS: development of an ambulatory assessment version of the EQ-5D-5L in an exploratory study.

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Background: Health fluctuations even within a single day are typical in multiple sclerosis (MS), but are not captured by widely used questionnaires like the EQ-5D-5L. This exploratory study aimed to develop an ambulatory assessment (AA) version of the EQ-5D-5L (EQ-5D-AA) where patients rate their health on mobile phones multiple times per day over several days,… Read more »

Validation of Computer-Adaptive Contrast Sensitivity as a Tool to Assess Visual Impairment in Multiple Sclerosis Patients

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Background: Impairment of visual function is one of the major symptoms of people with multiple sclerosis (pwMS). A multitude of disease effects including inflammation and neurodegeneration lead to structural impairment in the visual system. However, the gold standard of disability quantification, the expanded disability status scale (EDSS), relies on visual assessment charts. A more comprehensive… Read more »

Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation.

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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 »

Clinical Presentation and Disease Course of 37 Consecutive Cases of Progressive Multifocal Leukoencephalopathy (PML) at a German Tertiary-Care Hospital: A Retrospective Observational Study.

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Background: Progressive multifocal leukoencephalopathy (PML) caused by JCV is a rare but frequently fatal disease of the central nervous system, usually affecting immunocompromised individuals. Our study aims to expand the data on patient characteristics, diagnosis, clinical course, possible PML-directed treatment, and outcome of patients with PML at a German tertiary-care hospital. Methods:In this single-center observational… Read more »

Study protocol for a randomised controlled trial of a web-based behavioural lifestyle programme for emPOWERment in early Mulitiple Sclerosis (POWER@MS1).

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Introduction: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that mainly affects young adults. Uncertainty is a major psychological burden of the disease from diagnosis to prognosis, enhanced by the pressure to make early decisions on a diverse set of immunotherapies. Watchful waiting for 1-2 years while adapting goals… Read more »

Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis

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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 »

Development and evaluation of an interactive web-based decision-making programme on relapse management for people with multiple sclerosis (POWER@MS2)-study protocol for a randomised controlled trial.

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Introduction: Multiple sclerosis is a chronic inflammatory, degenerative disease of the central nervous system manifesting at first with relapses in about 85% of cases. In Germany, intravenous therapy with high-dose corticosteroids is the treatment standard of acute relapses. The treatment leads to a faster reduction of symptoms in about 25 of 100 treated patients but… Read more »

Enhancing mitochondrial activity in neurons protects against neurodegeneration in a mouse model of multiple sclerosis

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While transcripts of neuronal mitochondrial genes are strongly suppressed in central nervous system inflammation, it is unknown whether this results in mitochondrial dysfunction and whether an increase of mitochondrial function can rescue neurodegeneration. Here we show that predominantly genes of the electron transport chain are suppressed in inflamed mouse neurons resulting in impaired mitochondrial complex… Read more »

Exploring Adherence to First-Line and Second-Line Immunotherapies in Multiple Sclerosis: An Interview Study

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Background: Treatment adherence is fundamental in multiple sclerosis (MS) management. Adherence rates vary significantly between studies, ranging from 30% to almost 90%, depending on assessment method and medication type. This study aimed to identify patient-related categories associated with treatment modification or discontinuation in people with MS receiving either first- or second-line treatment. Methods: Semistructured interviews… Read more »

Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis

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Background: Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective: To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods: 36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during… Read more »

Construction of a User-Led Resource for People Transitioning to Secondary Progressive Multiple Sclerosis: Results of an Internation Nominal Group Study

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Background: ManTra is a mixed-methods, co-production research project for developing an intervention (resource) for people with newly diagnosed secondary progressive multiple sclerosis (pwSPMS) in Italy and Germany. In previous project actions, six resources were outlined, meeting the needs prioritized by pwSPMS. Aims: This study aims to achieve multiple-stakeholder consensus on the most suitable resource and… Read more »

Quality of Stroke Patient Information Applied in Randomized Controlled Trials-Literature Review

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Background: Strokes have a huge impact on patients‘ quality of life. Although there are potentially effective secondary preventions and treatment options for stroke patients, adherence is mostly low. Low disease and treatment-related knowledge and, consequently, a lack of informed decision-making in stroke patients may contribute to this problem. However, stroke patient information did not seem… Read more »

Heterogeneity of multiple sclerosis lesions in fast diffusional kurtosis imaging

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Background: Mean kurtosis (MK), one of the parameters derived from diffusion kurtosis imaging (DKI), has shown increased sensitivity to tissue microstructure damage in several neurological disorders. Methods: Thirty-seven patients with relapsing-remitting MS and eleven healthy controls (HC) received brain imaging on a 3T MR scanner, including a fast DKI sequence. MK and mean diffusivity (MD)… Read more »

Current and Long-Term Physical Activity Among Adults with Multiple Sclerosis in the United States: COM-B Variables as Explanatory Factors

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Background: Physical activity is an evidence-based, safe second-line approach for improved multiple sclerosis (MS) symptoms and disease progression. This study examined the contributions of Capability-Opportunity-Motivation-Behavior (COM-B) factors for understanding engagement in current and long-term physical activity among persons with MS in the United States (U.S.). Method: Adults with MS in the U.S. (N = 854)… Read more »

Impact of a multimedia website with patient experiences of multiple sclerosis (PExMS) on immunotherapy decision making: study protocol for a pilot randomised controlled trial in a mixed-methods design.

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Background: A variety of management options (e.g. immunotherapies, lifestyle interventions, and rehabilitation) are available for people with relapsing-remitting multiple sclerosis (RRMS). Besides coping with the diagnosis, people with MS (pwMS) have to make complex decisions such as deciding about immunotherapies. In addition to factual information, reports of patient experiences (PEx) may support patients in decision-making…. Read more »

Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

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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 severity in the setting of two multicenter cohort studies (n NationMS = 946, n BIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum… Read more »

Psychobehavioral Treatment Options for Sexual Dysfunction in Multiple Sclerosis: A Systematic Review

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Background: Sexual dysfunction in multiple sclerosis (MS) is a significant but overlooked impairment, and treatment options are rare. The aims of this systematic review were to identify psychological interventions used to treat sexual dysfunction in MS, to estimate their benefit, and to note appropriate treatment approaches for research projects and clinical use. Methods: A systematic… Read more »

„I will respect the Autonomy of My Patient“: A Scoping Review of Shared Decision Making in Multiple Sclerosis

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Background: Patient autonomy is a bioethical principle that was strengthened in the revised Declaration of Geneva. Shared decision making (SDM) is particularly relevant in the management of multiple sclerosis (MS) because many preference-sensitive decisions have to be made during the disease course. We aimed to summarize the available evidence on SDM in the MS field… Read more »

Blunted neural and psychological stress processing predicts future grey matter atrophy in multiple sclerosis.

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Background: Multiple sclerosis (MS) is characterized by two neuropathological key aspects: inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability. Methods: We tested whether neural network… Read more »

Transdiagnostic hippocampal damage patterns in neuroimmunological disorders

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Hippocampal damage and associated cognitive deficits are frequently observed in neuroimmunological disorders, but comparative analyses to identify shared hippocampal damage patterns are missing. Here, we adopted a transdiagnostic analytical approach and investigated hippocampal shape deformations and associated cognitive deficits in four neuroimmunological diseases. We studied 120 patients (n = 30 in each group), including patients… Read more »

A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice

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Among laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several transgenic mice carry a P2rx7… Read more »

Frequent neurocognitive deficits after recovery from mild COVID-19

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Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In… Read more »

Assessing the effect of an evidence-based patient online educational tool for people with multiple sclerosis called UMIMS-understanding magnetic resonance imaging in multiple sclerosis: study protocol for a double-blind, randomized controlled trial

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Background: While magnetic resonance imaging (MRI) plays a major role in the lives of people with multiple sclerosis (pwMS), studies have shown that MRI-specific knowledge in pwMS is limited. Moreover, poor knowledge was associated with negative feelings towards MRI (e.g. anxiety concerning MRI scan). Because information sources about MRI in MS for pwMS are not… Read more »

Patient autonomy in dentistry: demonstrating the role for shared decision making

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Background: Evidence-based practice, decision aids, patient preferences and autonomy preferences (AP) play an important role in making decisions with the patient. They are crucial in the process of a shared decision making (SDM) and can be incorporated into quality criteria for patient involvement in health care. However, there are few studies on SDM and AP… Read more »

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial

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Introduction: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention… Read more »

Voltage-Gated Proton Channel Hv1 Controls TLR9 Activation in Plasmacytoid Dendritic Cells

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The voltage-gated proton channel Hv1 regulates proton fluxes across membranes, thereby influencing pH-dependent processes. Plasmacytoid dendritic cells (pDCs) require a particularly tight regulation of endosomal pH to ensure strong type I IFN secretion exclusively during infection, avoiding autoimmunity. However, whether Hv1 is important for pH control in pDCs is presently unknown. In this study, we… Read more »

Long-term prognostic counselling in people with multiple sclerosis using an online analytical processing tool.

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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 »

Comprehension of confidence intervals in audio-visual patient information materials for people with multiple sclerosis (COCO-MS): A web-based randomised controlled, parallel group trial

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Objectives: To evaluate patient information materials on confidence intervals (CIs) in multiple sclerosis to be used with patient decision aids. Methods: Web-based randomised controlled parallel group trial with four study arms. Participants were equally allocated to one of three versions of audio-visual patient information or to a standard written information (arm IV). In the short… Read more »

Is APOE ε4 associated with cognitive performance in early MS?

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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 nucleotide polymorphisms rs429358 (ε4) and rs7412 (ε2)… Read more »

Conversion to secondary progressive multiple sclerosis: Multistakeholder experiences and needs in Italy

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Background: Conversion to secondary progressive multiple sclerosis (SPMS) is associated with a relatively poor prognosis, and SPMS is responsible for the majority of the social and economic costs associated with MS. Managing the Transition to SPMS (ManTra) is a mixed methods project conducted in Italy and Germany aimed to set up a user-led resource to… Read more »

Fatigue in Multiple Sclerosis Is Associated With Childhood Adversities

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Fatigue is a common and disabling symptom in patients with Multiple Sclerosis (PwMS). Its pathogenesis, however, is still not fully understood. Potential psychological roots, in particular, have received little attention to date. The present study examined the association of childhood adversities, specific trait characteristics, and MS disease characteristics with fatigue symptoms utilizing path analysis. Five… Read more »

Multiple sclerosis and physical activity: A German-wide survey on the behaviour, barriers and desires of those affected

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Background: Physical activity (PA) has beneficial effects on many disease related symptoms in people with multiple sclerosis (pwMS). Physical parameters – such as muscle strength, endurance, and balance – as wellas fatigue, depression and neurocognitive functioning, can be positively influenced by regular PA. Nevertheless, pwMS are less physically active than the general population. The reasons… Read more »

Smartphone Accelerometry: A Smart and Reliable Measurement of Real-Life Physical Activity in Multiple Sclerosis and Healthy Individuals

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Background: Mobility impairment is common in persons with multiple sclerosis (pwMS) and can be assessed with clinical tests and surveys that have restricted ecological validity. Commercial research-based accelerometers are considered to be more valuable as they measure real-life mobility. Smartphone accelerometry might be an easily accessible alternative. Objective: To explore smartphone accelerometry in comparison to… Read more »

Sex differences in brain atrophy in multiple sclerosis.

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Background: Women are more susceptible to multiple sclerosis (MS) than men by a ratio of approximately 3:1. However, being male is a risk factor for worse disability progression. Inflammatory genes have been linked to susceptibility, while neurodegeneration underlies disability progression. Thus, there appears to be a differential effect of sex on inflammation versus neurodegeneration. Further,… Read more »

Comorbid depression in medical diseases

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Depression is one of the most common comorbidities of many chronic medical diseases including cancer and cardiovascular, metabolic, inflammatory and neurological disorders. Indeed, the prevalence of depression in these patient groups is often substantially higher than in the general population, and depression accounts for a substantial part of the psychosocial burden of these disorders. Many… Read more »

TRPV4-mediated regulation of the blood brain barrier is abolished during inflammation

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Blood-brain barrier (BBB) dysfunction is critically involved in determining the extent of several central nervous systems (CNS) pathologies and here in particular neuroinflammatory conditions. Inhibiting BBB breakdown could reduce the level of vasogenic edema and the number of immune cells invading the CNS, thereby counteracting neuronal injury. Transient receptor potential (TRP) channels have an important… Read more »

Aerobic Exercise Induces Functional and Structural Reorganization of CNS Networks in Multiple Sclerosis: A Randomized Controlled Trial

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Objectives: Evidence from animal studies suggests that aerobic exercise may promote neuroplasticity and could, therefore, provide therapeutic benefits for neurological diseases such as multiple sclerosis (MS). However, the effects of exercise in human CNS disorders on the topology of brain networks, which might serve as an outcome at the interface between biology and clinical performance,… Read more »

Genetic determinants of the humoral immune response in MS

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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)…. Read more »

Contribution of NAADP to Glutamate-Evoked Changes in CA2+ Homeostasis in Mouse Hippocampal Neurons

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Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such as TRPML1, the (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels as well as Ryanodine Receptors type 1…

Motor neuron translatome reveals deregulation of SYNGR4 and PLEKHB1 in mutant TDP-43 amyotrophic lateral sclerosis mutants

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Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease with progressive loss of motor neuron (MN) function in the brain and spinal cord. Mutations in TARDBP, encoding the RNA-binding protein TDP-43, are one cause of ALS and TDP-43 mislocalization in MNs is a key pathological feature of > 95% of ALS cases. While numerous studies… Read more »

Distinct Functional Connectivity Signartures of Impaired Social Cognition in Multiple Sclerosis

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Objective: Multiple sclerosis (MS) is characterized by impairments in basic cognitive functions such as information processing speed as well as in more complex, higher-order domains such as social cognition. However, as these deficits often co-occur, it has remained challenging to determine whether they have a specific pathological basis or are driven by shared biology. Methods:… Read more »

Control of SARS-CoV-2 infection in rituximab-treated neuroimmunological patients.

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Individuals with autoimmune diseases, such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), that require long-term immunosuppression are regarded as particularly vulnerable in the current COVID-19 pandemic. However, few details about the effect of individual immunotherapies have been reported, which could instruct us about the immunological control of severe acute respiratory syndrome coronavirus… Read more »

Statins in the treatment of depression: Hype or Hope?

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Many patients with depression do not respond sufficiently to antidepressant treatment, necessitating other treatment approaches. HMG-CoA reductase inhibitors (i.e. statins), which are frequently used for their cardioprotective properties, have also been studied regarding potential antidepressant effects. Possible mechanisms underlying an antidepressant effect of statins may include the anti-inflammatory, antioxidant and lipid lowering properties of this… Read more »

Feasibility of a smartphone app to enhance physical activity in progressive MS: a pilot randomized controlled pilot trial over three months.

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Background: People with chronic progressive multiple sclerosis (CPMS) have limited options in medical treatment. Enhancing physical activity (PA) might promote neuroregeneration in multiple sclerosis (MS) and positively influence disability, thus providing an alternative to medical treatment. Previous studies indicate that evidence-based patient information (EBPI) is essential for inducing behavioral change, e.g. enhancing PA. Objective: To… Read more »

An Automated and High-Throughput-Screening Compatible Pluripotent Stem Cell-Based Test Platform for Developmental and Reproductive Toxicity Assessment of Small Molecule Compounds

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The embryonic stem cell test (EST) represents the only validated and accepted in vitro system for the detection and classification of compounds according to their developmental and reproductive teratogenic potency. The widespread implementation of the EST, however, in particular for routine application in pharmaceutical development, has not been achieved so far. Several drawbacks still limit… Read more »

Heterogeneity of Response to Immune Checkpoint Blockade in Hypermutated Expermimental Gliomas

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Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental… Read more »

Dietary Tryptophan Links Encephalogenicity of Autoreactive T Cells With Gut Microbial Ecology

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The interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid – tryptophan – from the diet abrogates CNS autoimmunity in a mouse model… Read more »

Lipid Mediator Profiles Predict Response to Therapy With an Oral Frankincense Extract in Relapsing-Remitting Multiple Sclerosis

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Lipid mediators (LMs) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts. We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis (RR-MS) patients who took a standardised frankincense extract (SFE) daily for eight months in a clinical phase IIa trial (NCT01450124) and in… Read more »

Clinical Implications of Serum Neurofilament in Newly Diagnosed MS Patients: A Longitudinal Multicentre Cohort Study

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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 syndrome (CIS) were recruited between August 2010 and November… Read more »

Medication beliefs in first-line and second-line treated multiple sclerosis patients

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Background: Immune treatments of multiple sclerosis (MS) can be classified in first-line and second-line approaches. While in both treatment efficacy is often not easy to assess in the short-term, treatment and illness beliefs may differ in first-line and second-line treated patients. The current study aimed to assess differential beliefs about medicine and illness perception between… Read more »

Exercise training and cognitive performance in persons with multiple sclerosis: A systematic review and multilevel meta-analysis of clinical trials.

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BACKGROUND: Cognitive impairment is common, debilitating, and poorly managed in persons with multiple sclerosis (pwMS). Exercise training might have positive effects on cognitive performance in pwMS, yet the overall magnitude, heterogeneity, and potential moderators remain unclear. OBJECTIVE: This three-level meta-analysis aims to identify the effects of exercise training and those of exercise modalities on global… Read more »

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis.

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OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with… Read more »

[Autologous hematopoietic stem cell transplantation for autoimmune diseases : Current indications and mode of action, a review on behalf of the EBMT Autoimmune Diseases Working Party (ADWP)].

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The recent introduction of biologic and targeted synthetic disease-modifying drugs has led to more specificity in the treatment of autoimmune diseases; however, they require continuous or intermittent administration, are associated with cumulative risks for side effects, result in high costs and provide no cure. In contrast, high-dose chemotherapy followed by transplantation of autologous hematopoietic stem… Read more »

A novel neurodegenerative spectrum disorder in patients with MLKL deficiency.

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Mixed lineage kinase domain-like (MLKL) is the main executor of necroptosis, an inflammatory form of programmed cell death. Necroptosis is implicated in combating infections, but also in contributing to numerous other clinical conditions, including cardiovascular diseases and neurodegenerative disorders. Inhibition of necroptosis is therefore of therapeutic interest. Here we report two siblings both of whom… Read more »

Challenges and lessons learned from using anchoring vignettes to explore quality of liefe response behavior

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PURPOSE: Asking patients to rate health-related quality of life (HRQoL) of hypothetical individuals described in anchoring vignettes has been proposed to enhance knowledge on how patients understand and respond to HRQoL questionnaires. In this article, we describe the development of anchoring vignettes and explore their utility for measuring response shift in patients‘ self-reports of HRQoL…. Read more »

Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study.

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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 determinants of pain in MS. To… Read more »

The Myelin Water Fraction Serves as a Marker for Age-Related Myelin Alterations in the Cerebral White Matter – A Multiparametric MRI Aging Study.

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Quantitative MRI modalities, such as diffusion tensor imaging (DTI) or magnetization transfer imaging (MTI) are sensitive to the neuronal effects of aging of the cerebral white matter (WM), but lack the specificity for myelin content. Myelin water imaging (MWI) is highly specific for myelin and may be more sensitive for the detection of changes in… 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.

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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 »

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

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Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address… Read more »

Functional and structural connectivity substrates of cognitive performance in relapsing remitting multiple sclerosis with mild disability.

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Multiple Sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), which can lead to severe cognitive impairment over time. Magnetic resonance imaging (MRI) is currently the best available biomarker to track MS pathophysiology in vivo and examine the link to clinical disability. However, conventional MRI metrics have… Read more »

Is multiple sclerosis progression associated with the HLA-DR15 haplotype?

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Background: The prevalence of multiple sclerosis is associated with the major histocompatibility complex class II DR15 haplotype HLA-DRB1*15:01∼HLA-DRB5*01:01. Objective: To assess whether multiple sclerosis progression is associated with the main susceptibility haplotype HLA-DRB1*15:01∼HLA-DRB5*01:01. Methods: Patients (n = 1230) and healthy controls (n = 2110) were genotyped for HLA-DRB1 and HLA-DRB5. The baseline Expanded Disability Status Scale (EDSS) score was… Read more »

Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders.

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OBJECTIVE:To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks. METHODS: A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies… Read more »

Recall of health-related quality of life: how does memory affect the SF-6D in patients with psoriasis or multiple sclerosis? A prospective observational study in Germany.

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OBJECTIVE:This study aimed to quantify recall bias in the measurement of health-related quality of life (HRQoL), that is, the extent to which recollection is impaired and leads to distorted judgements.DESIGN:Prospective observational study.SETTING AND PARTICIPANTS:One hundred patients with two paradigmatic chronic diseases (50 with multiple sclerosis and 50 with psoriasis) were recruited at two outpatient clinics.METHODS… Read more »

Age-Related Measurements of the Myelin Water Fraction derived from 3D multi-echo GRASE reflect Myelin Content of the Cerebral White Matter.

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Myelin Water Fraction (MWF) measurements derived from quantitative Myelin Water Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM) microstructure. Here, we investigated age-related alterations of the MWF in normal aging brains of healthy volunteers utilizing two fast and clinically feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and… Read more »

T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis.

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Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we characterize immunomodulation at the single-clone level by sequencing the T cell… Read more »

History of fatigue in multiple sclerosis is associated with grey matter atrophy.

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Fatigue in multiple sclerosis (MS) has been associated with brain damage with low replicability. Temporal fatigue fluctuations have not been considered. We assessed whether sustained fatigue (SF) associates more strongly with grey matter (GM) changes than reversible fatigue (RF). Patients were stratified into three groups according to historical fatigue levels: SF (n = 30, i.e. patients who… Read more »

Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS

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OBJECTIVE: To investigate the effects of natalizumab (NAT) treatment on intrathecally produced antiviral antibodies in MS. METHODS: We performed a longitudinal, observational study analyzing both serum and CSF samples collected before and during NAT treatment for antibodies against measles, rubella, mumps, influenza, entero, herpes, and polyoma viruses, including JC polyomavirus (JCV) and its nearest homologue… Read more »

Conversion to Secondary Progressive Multiple Sclerosis: Patient Awareness and Needs. Results From an Online Survey in Italy and Germany.

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Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature… Read more »

Healthy women with severe early life trauma show altered neural facilitation of emotion inhibition under acute stress.

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Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations… Read more »

Pregnancy Enables Expansion of Disease-Specific Regulatory T Cells in an Animal Model of Multiple Sclerosis.

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Disease activity of autoimmune disorders such as multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to nonspecific immunomodulation or mediated by Ag-specific regulation of disease-causing conventional T cells (Tcon) and immunosuppressive regulatory T cells (Tregs) remains elusive. In the current study, we… Read more »

Developing a fall prevention program: what are the views and opinions of people with multiple sclerosis?

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Purpose: Falls are common in people with multiple sclerosis (MS), yet there are a few targeted fall prevention programs. Existing programs report a high dropout rate and a low adherence, which may be due to a mismatch between program characteristics and participants preferences. To clarify a possible discrepancy, this study investigates the views and opinions… Read more »

Neuronal vulnerability and multilineage diversity in multiple sclerosis.

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Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in… Read more »

Diagnostics and treatment of tuberculosis under immunotherapy for multiple sclerosis : Current status and recommendations in Germany.

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After years of low incidence, a large increase of new tuberculosis (TB) cases has been reported in Germany since 2015. New immunotherapies for the treatment of multiple sclerosis (MS) are associated with a reduced immune competence and a potential increased risk for infections. Most neurologists lack specific experiences with TB infections. This article summarizes specific… Read more »

Long-term physical activity in people with multiple sclerosis: exploring expert views on facilitators and barriers.

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PURPOSE: To explore the views of experts on facilitators and barriers of long-term physical activity among people with multiple sclerosis living in different European countries. METHODS: We conducted semi-structured telephone or face to face interviews with twelve multiple sclerosis and physical activity experts (scientists, practitioners, patient representatives) from five European countries. Interviews were audio-recorded, transcribed… Read more »

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk.

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Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual… Read more »

Predictors of response and remission in a naturalistic inpatient sample undergoing multimodal treatment for depression.

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BACKGROUND: Many depressed patients do not achieve response or remission despite adequate treatment. Identifying predictors of outcome can contribute to developing therapeutic algorithms for difficult-to-treat depression. Therefore, we examined clinical predictors of response and remission in a naturalistic inpatient sample undergoing multimodal treatment for depression. METHODS: Three hundred and fifty-one consecutive inpatients admitted to a… Read more »

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

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The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer’s disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity,… Read more »

Spectrally fat-suppressed coronal 2D TSE sequences may be more sensitive than 2D STIR for the detection of hyperintense optic nerve lesions.

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OBJECTIVES: The aim of the study is to compare coronal spectrally fat-suppressed 2D turbo spin-echo (TSE) with 2D short-tau inversion-recovery (STIR) sequences for the detection of optic nerve hyperintensities in patients with acute optic nerve neuritis (ON). METHODS: A retrospective review of patients with suspected unilateral ON and pathological visual evoked potentials, who received coronal… Read more »

Towards patients‘ understanding of health-related quality of life-a mixed-method study in psoriasis and multiple sclerosis.

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PURPOSE: Patients‘ individual understanding of health-related quality of life (HRQoL) varies widely, making the measurement of this complex and subjective construct challenging. Anchoring vignettes, i.e., descriptions of fictive patients may provide insights into patients‘ individual questionnaire reference frames, assessment processes, and understanding of HRQoL. This study analyzes how patients assess HRQoL of vignettes. METHODS: This… Read more »

Neural mechanisms of perceptual decision-making and their link to neuropsychiatric symptoms in multiple sclerosis.

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BACKGROUND: Decision-making (DM) capabilities are impaired in multiple sclerosis (MS). A variety of researchers hypothesized that this impairment is associated with reduced quality of life (QoL) and neuropsychiatric symptoms. Studies explicitly testing this hypothesis, however, are rare, provided inconclusive results, or evaluated only a limited selection of DM domains. Consequently, we conducted the first MS… Read more »

Reasons for delayed admission after stroke: results of a qualitative and quantitative survey.

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Background: Acute stroke treatment shows time-dependent benefit to prevent disability. Public information campaigns and streamlining of emergency management have been performed, but still, only one-third of acute stroke patients are admitted >4.5 hrs after symptom onset. Patients and methods: We interviewed 15 patients, presenting >4.5 hrs after symptom onset, regarding symptom recognition, emotions and their… Read more »

Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice.

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Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), for example, multiple sclerosis (MS). Intravenous MSC transplantation was reported to… Read more »

The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): results from the German validation study.

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BACKGROUND: Recent research has convincingly shown that the ability to work mainly depends on the cognitive status in multiple sclerosis (MS). An international committee of experts recommended a brief neuropsychological battery to evaluate cognitive performance in MS. BICAMS comprises three tests, the Symbol Digit Modalities Test (SDMT), the learning trials of the California Verbal Learning… Read more »

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

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BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe… Read more »

Risk knowledge of people with relapsing-remitting multiple sclerosis – Results of an international survey

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BACKGROUND: Adequate disease and treatment-related risk knowledge of people with Multiple Sclerosis (pwMS) is a prerequisite for informed choices in medical encounters. Previous work showed that MS risk knowledge is low among pwMS and role preferences are different in Italy and Germany. OBJECTIVE: We investigated the level of risk knowledge and role preferences in 8… Read more »

In search of distinct MS-related fatigue subtypes: results from a multi-cohort analysis in 1.403 MS patients.

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Fatigue is among the most disabling symptoms in patients with multiple sclerosis (PwMS). The common distinction between cognitive and motor fatigue is typically incorporated in self-rating instruments, such as the Chalder Fatigue Questionnaire (CFQ), the Fatigue Scale for Motor and Cognitive Functions (FSMC) or the Modified Fatigue Impact Scale (MFIS). The present study investigated the… Read more »

Bassoon proteinopathy drives neurodegeneration in multiple sclerosis.

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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 »

Relapse rates and long-term outcome in primary angiitis of the central nervous system.

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OBJECTIVE: To analyze the treatment response in patients with primary angiitis of the central nervous system (PACNS). METHODS: In a single-center retrospective observational study, we assessed relapses, remission, and long-term outcome by use of the modified Rankin Scale (mRS) under different immunotherapies. Eligible patients had CNS biopsy in favor of PACNS or neuroimaging compatible with… Read more »

Impairment and restrictions in possibly benign multiple sclerosis.

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OBJECTIVE: The aim was to describe a broad range of health dimensions in possibly benign multiple sclerosis (MS) hypothesizing that despite some limitations there is a high adaptation to the disease. METHODS: All patients from an outpatient university clinic data registry with an Expanded Disability Status Scale (EDSS) ≤3.5 and disease duration ≥15 years were… Read more »

Development of Cortical Lesion Volumes on Double Inversion Recovery MRI in Patients With Relapse-Onset Multiple Sclerosis.

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Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients‘ disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of… Read more »

Emotions towards magnetic resonance imaging in people with multiple sclerosis.

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OBJECTIVES: People with multiple sclerosis (pwMS) often have magnetic resonance imaging (MRI) examinations. While MRI can help guide MS management, it may be a source of anxiety for pwMS. We aimed to develop and validate a questionnaire on the „EMotions and Attitudes towards MRI“ (MRI-EMA). MATERIAL & METHODS: The questionnaire was developed, tested in 2… Read more »

Arc/Arg3.1 defines dendritic cells and Langerhans cells with superior migratory ability independent of phenotype and ontogeny in mice

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The key function of migratory dendritic cells (migDCs) is to take up antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate immune responses. Recently, we discovered that in the mouse immune system activity-regulated cytoskeleton associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) is exclusively expressed by migDCs and is a central driver of fast… Read more »

Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life.

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Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+CD4+CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression… Read more »

Severe meningo-/encephalitis after daclizumab therapy for multiple sclerosis.

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BACKGROUND: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018.OBJECTIVE AND METHODS: This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after… Read more »

Benefit evaluation in multiple sclerosis relapse treatment from the patients‘ perspective – Development and validation of a new questionnaire

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BACKGROUND: Little is known on how to measure patient-relevant benefit of relapse treatment in relapsing-remitting multiple sclerosis (MS). The objective of this study was to develop and validate a new method for monitoring recovery from MS relapses and patient-relevant treatment benefits. METHODS: A 27-item questionnaire was developed using a multi-step approach comprising open item collection,… Read more »

Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS).

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BACKGROUND: Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis. METHODS: Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS… Read more »

Progesterone modulates the T cell response via glucocorticoid receptor-dependent pathways.

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PROBLEM: Steroid hormones such as progesterone and glucocorticoids rise during pregnancy and are accountable for the adaptation of the maternal immune system to pregnancy. How steroid hormones induce fetal tolerance is not fully understood. We hypothesized that steroid hormones selectively regulate the T cell response by promoting T cell death. METHOD OF STUDY: We incubated… Read more »

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder.

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Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of… Read more »

Distribution of brain sodium long and short relaxation times and concentrations: a multi-echo ultra-high field 23Na MRI study.

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Sodium (23Na) MRI proffers the possibility of novel information for neurological research but also particular challenges. Uncertainty can arise in in vivo 23Na estimates from signal losses given the rapidity of T2* decay due to biexponential relaxation with both short (T2*short) and long (T2*long) components. We build on previous work by characterising the decay curve… Read more »

Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial.

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Background: Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in multiple sclerosis. Objective and Methods: This randomized controlled trial with 34 patients in the intervention group (IG) (mean: 38.2 years (±9.6)) and 34 patients in the control group (CG) (mean: 39.6 years (±9.7)) aimed to determine the effects of aerobic… Read more »

Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis.

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We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p = 1.22 × 10-17 , OR = 13.66 [7.50-24.87]). Potential associations, below genome-wide significance, were found with rs72961463 close… Read more »

Age-Related Measurements of the Myelin Water Fraction derived from 3D multi-echo GRASE reflect Myelin Content of the Cerebral White Matter.

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Myelin Water Fraction (MWF) measurements derived from quantitative Myelin Water Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM) microstructure. Here, we investigated age-related alterations of the MWF in normal aging brains of healthy volunteers utilizing two fast and clinically feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and… Read more »