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 »

Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions.

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Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide… Read more »

Prognostic information for people with MS: Impossible or inevitable?

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Delivering prognostic information is a challenging issue in medicine and has been largely neglected in the past. A major reason has been a suspected nocebo effect of pessimistic estimates, although this is largely unproven. Among people with multiple sclerosis (MS), there is a strong unmet need to receive long-term prognostic information. This viewpoint discusses reasons… Read more »

Sex differences in autoimmune disorders of the central nervous system.

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Stronger adaptive immune responses in females can be observed in different mammals, resulting in better control of infections compared to males. However, this presumably evolutionary difference likely also drives higher incidence of autoimmune diseases observed in humans. Here, we summarize sex differences in the most common autoimmune diseases of the central nervous system (CNS) and… Read more »

Information provision for people with multiple sclerosis.

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BACKGROUND: People with multiple sclerosis (MS) are confronted with a number of important uncertainties concerning many aspects of the disease. Among others, these include diagnosis, prognosis, disease course, disease-modifying therapies, symptomatic therapies and non-pharmacological interventions. It has been shown that people with MS demand adequate information to be able to actively participate in medical decision… Read more »

Differences in diffusion tensor imaging changes between narcolepsy with and without cataplexy.

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OBJECTIVE: The distinctive clinical finding of Type 1 narcolepsy compared to Type 2 is the presence of cataplexy. Several neuroimaging studies have also reported abnormalities in narcolepsy patients with or without cataplexy. However, there are conflicting results to differentiate them. In this study, we aimed to clarify the white matter changes in narcolepsy patients both… Read more »

Magnetic resonance imaging as a prognostic disability marker in clinically isolated syndrome: A systematic review.

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Magnetic resonance imaging (MRI) is the key prognostic tool in people with a clinically isolated syndrome (CIS). There is increasing interest in treating people following a CIS in the hope that conversion to multiple sclerosis (MS) will be prevented and future disability reduced. So far, the prognostic value of MRI for disability following a CIS… Read more »

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood.

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Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast,… Read more »

Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring.

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Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the… Read more »

Causal interpretation of correlational studies – Analysis of medical news on the website of the official journal for German physicians

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BACKGROUND: Media frequently draws inappropriate causal statements from observational studies. We analyzed the reporting of study results in the Medical News section of the German medical journal Deutsches Ärzteblatt (DÄ). METHODS: Study design: Retrospective quantitative content analysis of randomly selected news reports and related original journal articles and press releases. A medical news report was… Read more »

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.

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BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic… Read more »

Treatment choices and neuropsychological symptoms of a large cohort of early MS.

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Objective: To assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS. Methods: The German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline… Read more »

Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis

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Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. METHODS: Patients with… Read more »

T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder.

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While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For… Read more »

Sexual dysfunctions in MS in relation to neuropsychiatric aspects and its psychological treatment: A scoping review.

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OBJECTIVE: Sexual dysfunction in multiple sclerosis (MS) is a significant, but often underestimated and overlooked suffering. Interventions to treat sexual dysfunction in MS are rare. The relation between sexual dysfunction in MS and psychological as well as neuropsychological aspects is evident. However, this field of research remains markedly underdeveloped in this severe chronic illness. The… Read more »

Does cladribine have an impact on brain atrophy in people with relapsing remitting multiple sclerosis?

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In their paper, De Stefano et al. Describe the reduction of the percentage brain volume change (PBVC) in patients with relapsing remitting multiple sclerosis (RRMS treated with the purine analog cladribine over a period of 24 months. While we highly appreciate the aim of looking at atrophy rates in new MS treatments, we would like… Read more »

Production of IL-17 by MAIT Cells Is Increased in Multiple Sclerosis and Is Associated with IL-7 Receptor Expression.

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Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17…. Read more »

Perceptions on the value of bodily functions in multiple sclerosis.

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BACKGROUND: In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians‘ perceptions. METHODS: In a multicenter… Read more »

A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial).

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OBJECTIVE: To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated… Read more »

The use of multiparametric quantitative magnetic resonance imaging for evaluating visually assigned lesion groups in patients with multiple sclerosis.

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In multiple sclerosis (MS), inflammatory lesions present a broad spectrum of histopathologic processes. For a better discrimination, lesions are visually defined into different lesion groups according to their appearance on conventional magnetic resonance imaging (MRI). The aim of this study was to investigate the properties of different MS lesion groups using multiparametric quantitative MRI. 35… Read more »

T1w dark blood imaging improves detection of contrast enhancing lesions in multiple sclerosis.

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PURPOSE: In multiple sclerosis (MS) the sensitivity for detection of contrast enhancing lesions (CEL) in T1-weighted scans is essential for diagnostics and therapy decisions. The purpose of our study was to evaluate the sensitivity of T1w MPRAGE scans in comparison to T1w dark blood technique (T1-DB) for CEL in MS. MATERIALS AND METHODS: 3T MR… Read more »

Aberrant peak lactate response in MS.

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BACKGROUND: The peak blood lactate response to an exhaustive exercise test in a number of chronic conditions has been shown to differ from that seen in healthy, untrained individuals. However, this has not been investigated for patients with multiple sclerosis (MS). OBJECTIVE: The main objective was to determine and compare the peak blood lactate response… Read more »

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

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BACKGROUND: Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The „nurse decision coach model“ was developed to redistribute health professionals‘ tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. OBJECTIVES: To test the feasibility of a decision coaching… Read more »

What should a person with relapsing-remitting multiple sclerosis know? – Focus group and survey data of a risk knowledge questionnaire (RIKNO 2.0).

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BACKGROUND: Risk knowledge is relevant to make informed decisions in multiple sclerosis (MS). The risk knowledge questionnaire for relapsing-remitting MS (RIKNO 1.0) was developed and piloted in Germany. OBJECTIVE: To produce a revised RIKNO 2.0 questionnaire using mixed methodology in a European setting. METHODS: The questionnaire was translated in seven languages. MS patient and health… Read more »

Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity.

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Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apoptotic death of immature T cells, and we have previously shown that… Read more »

Acute and long-term effects of fingolimod on heart rhythm and heart rate variability in patients with multiple sclerosis.

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BACKGROUND: Fingolimod can lead to increased risk of cardiac events such as bradycardia or atrioventricular (AV) block. OBJECTIVE: Evaluate acute and long-term effects of fingolimod on heart rhythm (HR), heart rate variability (HRV) and development of AV-blocks. METHODS: In 64 patients with relapsing-remitting multiple sclerosis Holter ECG monitoring (HEM) and HRV analysis were performed 24h… Read more »

Low clinical conversion rate in clinically isolated syndrome (CIS) patients – diagnostic benefit of McDonald 2010 criteria?

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BACKGROUND: New diagnostic criteria of Multiple Sclerosis (MS) increase the number of patients being diagnosed with MS while a substantial part might not convert to clinically definite MS (CDMS). OBJECTIVE: Diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom a MS… Read more »

Effect of informed consent on patient characteristics in a stroke thrombolysis trial.

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OBJECTIVE: To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials. METHODS: We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based… Read more »

Managing the transition (ManTra): a resource for persons with secondary progressive multiple sclerosis and their health professionals: protocol for a mixed-methods study in Italy.

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INTRODUCTION: 15 years after clinical onset, about 50% of patients with relapsing-remitting multiple sclerosis convert to secondary progressive multiple sclerosis (SPMS). Notwithstanding the importance of this transition, knowledge of the experiences and needs of patients and carers is fragmentary, and targeted interventions are not available. Managing the Transition to SPMS (ManTra) is a mixed methodology… Read more »

Reduced rich-club connectivity is related to disability in primary progressive MS.

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OBJECTIVE: To investigate whether the structural connectivity of the brain’s rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures. METHODS: We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were… Read more »

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response.

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OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from… Read more »

Exercise in patients with multiple sclerosis.

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Exercise can be a beneficial rehabilitation strategy for people with multiple sclerosis to manage symptoms, restore function, optimise quality of life, promote wellness, and boost participation in activities of daily living. However, this population typically engages in low levels of health-promoting physical activity compared with adults from the general population, a fact which has not… Read more »

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

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BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study… Read more »

Numeracy of multiple sclerosis patients: A comparison of patients from the PERCEPT study to a German probabilistic sample.

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OBJECTIVE: A shared decision-making approach is suggested for multiple sclerosis (MS) patients. To properly evaluate benefits and risks of different treatment options accordingly, MS patients require sufficient numeracy – the ability to understand quantitative information. It is unknown whether MS affects numeracy. Therefore, we investigated whether patients‘ numeracy was impaired compared to a probabilistic national… Read more »

Brain activity, regional gray matter loss, and decision-making in multiple sclerosis.

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BACKGROUND: Decision-making (DM) abilities deteriorate with multiple sclerosis (MS) disease progression which impairs everyday life and is thus clinically important. OBJECTIVE: To investigate the underlying neurocognitive processes and their relation to regional gray matter (GM) loss induced by MS. METHODS: We used a functional magnetic resonance imaging (fMRI) Iowa Gambling Task to measure DM-related brain… Read more »

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders.

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BACKGROUND: Gender and age at onset are important epidemiological factros influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. OBJECTIVE: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response attack treatment in patients with neuromyelitis optica (NMO) and its sprectrum disorders (neuromeyelitis optica spectrum disorder… Read more »

Training doctors briefly and in situ to involve their patients in making medical decisions-Preliminary testing of a newly developed module.

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OBJECTIVE: To carry out preliminary evaluation of a training module for doctors to enhance their ability to involve their patients in medical decision making. The training refers to the shared decision-making (SDM) communication concept. METHODS: The training module includes a comprehensive manual, a corresponding video tutorial with communication examples and a 15-minute face-to-face feedback session… Read more »

No relevant impact of ambient temperature on disability measurements in a large cohort of patients with multiple sclerosis.

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BACKGROUND AND PURPOSE: Many patients with multiple sclerosis (MS) report a worsening of symptoms due to high ambient temperatures, but objective data about this association are rare and contradictory. The aim of this study was to investigate the influence of ambient temperature on standard clinical tests. METHODS: We extracted the Symbol Digit Modality Test, Nine… Read more »

Is the risk of progressive multifocal leukoencephalopathy the real reason for Natalizumab discontinuation in patients with multiple sclerosis?

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BACKGROUND: Progressive multifocal Leukoencephalopathy (PML) is one of the major risks of natalizumab therapy. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing. OBJECTIVES: We addressed the following questions: How do natalizumab-treated multiple sclerosis patients and their treating physicians assess and deal with PML risk?… Read more »

Benefit-risk perception of natalizumab therapy in neurologists and a larger cohort of multiple sclerosis patients

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BACKGROUND: Natalizumab (NAT) is associated with the risk of progressive multifocal leukoencephalopathy (PML). Risk stratification algorithms have been developed, however, without detectable reduction of PML incidence. OBJECTIVE: To evaluate to which extent patients and physicians understand and accept risks associated with NAT treatment. METHODS: Prospective observational cohort study in German MS centers (n=73) among NAT-treated… Read more »

Control conditions for randomised trials of behavioural interventions in psychiatry: a decision framework.

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In psychiatry, comparative analyses of therapeutic options and the aggregation of data from clinical trials across different therapeutic approaches play an important role in clinical decision making, treatment guidelines, and health policy. This approach assumes that trials of pharmacological and behavioural therapies generally produce the same level of evidence when properly designed. However, trial design… Read more »

Patient education for people with multiple sclerosis-associated fatigue: A systematic review.

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BACKGROUND: Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease often causing decreased quality of life, social withdrawal and unemployment. Studies examining the effect of pharmacological interventions demonstrated only minor effects, whereas non-pharmacological interventions as e.g. patient education programs have shown promising results. OBJECTIVE: We aim to systematically review the literature to determine the effect… Read more »

Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS.

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Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab treatment in patients with relapsing-remitting MS (RRMS)1 with 638 confirmed cases as of March 2016. Therapeutic re-establishment of cerebral immune surveillance in PML management is complicated by immune reconstitution inflammatory syndrome (IRIS), an exuberant inflammatory response that aggravates damage caused by John Cunningham virus (JCV)… Read more »

Ruxolitinib treatment in a patient with neuromyelitis optica: A case report.

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Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune demyelinating disease of the CNS that predominantly affects the optic nerves and the spinal cord.1 Because of the severity and poor recovery of attacks, aggressive immunosuppressive agents are used early in the clinical course to reduce relapse frequency. Apart from classical immunosuppressant agents, biologicals such… Read more »

Reliability of cortical lesion detection on double inversion recovery MRI applying the MAGNIMS-Criteria in multiple sclerosis patients within a 16-months period.

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PURPOSE: In patients with multiple sclerosis (MS), Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to identify cortical lesions (CL). We sought to evaluate the reliability of CL detection on DIR longitudinally at multiple subsequent time-points applying the MAGNIMs scoring criteria for CLs. METHODS: 26 MS patients received a 3T-MRI (Siemens, Skyra)… Read more »

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis.

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BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with… Read more »

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing-remitting MS.

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BACKGROUND: Neurodegeneration in multiple sclerosis (MS) may be investigated in the visual system as optical coherence tomography (OCT) and magnetic resonance imaging (MRI) allows examining structural integrity in detail. The association between thickness of retinal layers and focal cortical volumes beyond the primary visual system has not been thoroughly investigated. OBJECTIVE: o investigate the association… Read more »

A new graphical format to communicate treatment effects to patients-A web-based randomized controlled trial.

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OBJECTIVE: Patients making treatment decisions require understandable evidence-based information. However, evidence on graphical presentation of benefits and side-effects of medical treatments is not conclusive. The study evaluated a new space-saving format, CLARIFIG (clarifying risk figures), aiming to facilitate accuracy of comprehension. METHODS: CLARIFIG displays groups of patients with and without treatment benefits as coloured sectors… Read more »

Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy

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Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy… Read more »

Activity of NaV1.2 promotes neurodegeneration in an animal model of multiple sclerosis

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Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along… Read more »

Insufficient treatment of severe depression in neuromyelitis optica sepctrum disorder

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OBJECTIVE: To investigate depression frequency, severity, current treatment, and interactions with somatic symptoms among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS:In this dual-center observational study, we included 71 patients diagnosed with NMOSD according to the International Panel for NMO Diagnosis 2015 criteria. The Beck Depression Inventory (BDI) was classified into severe, moderate, or minimal/no… Read more »

Dietary Interventions in Multiple Sclerosis: Development and Pilot-Testing of an Evidence Based Patient Education Program

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BACKGROUND: Dietary factors have been discussed to influence risk or disease course of multiple sclerosis (MS). Specific diets are widely used among patients with MS. OBJECTIVE: To design and pilot-test an evidence based patient education program on dietary factors in MS. METHODS: We performed a systematic literature search on the effectiveness of dietary interventions in… Read more »

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis.

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Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI… Read more »

Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

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Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV) daily for three days, or a placebo,… Read more »

Introducing a new method to assess vision: Computer-adaptive contrast-sensitivity testing predicts visual functioning better than charts in multiple sclerosis patients

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Background: Impaired low-contrast visual acuity (LCVA) is common in multiple sclerosis (MS) and other neurological diseases. Its assessment is often limited to selected contrasts, for example, 2.5% or 1.25%. Computerized adaptive testing with the quick contrast-sensitivity function (qCSF) method allows assessment across expanded contrast and spatial frequency ranges. Objective: The objective of this article is… Read more »

Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting.

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BACKGROUND: Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements… Read more »

Comprehension of confidence intervals – development and piloting of patient information materials for people with multiple sclerosis: qualitative study and pilot randomised controlled trial

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BACKGROUND: Presentation of confidence intervals alongside information about treatment effects can support informed treatment choices in people with multiple sclerosis. We aimed to develop and pilot-test different written patient information materials explaining confidence intervals in people with relapsing-remitting multiple sclerosis. Further, a questionnaire on comprehension of confidence intervals was developed and piloted. METHODS: We developed… Read more »

Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation

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Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activityregulated… Read more »

Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis.

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Background: Clinical studies have suggested beneficial effects of exercise on cognitive function in ageing adults and neurodegenerative diseases such as dementia. Recent work indicates the same for progressive multiple sclerosis (MS), an inflammatory and degenerative disease of the central nervous system (CNS). The biological pathways associated with these effects are however not well understood. Objective:… Read more »

Major depressive disorder.

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Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is… Read more »

Subjective and objective knowledge and decisional role preferences in cerebrovascular patients compared to controls.

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BACKGROUND: Risk knowledge and active role preferences are important for patient involvement in treatment decision-making and adherence. Although knowledge about stroke warning signs and risk factors has received considerable attention, objective knowledge on secondary prevention and further self-esteem subjective knowledge have rarely been studied. The aim of our study was to investigate knowledge and treatment… Read more »

Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application.

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Translational research generally refers to a „bench to bedside“ approach where basic science discoveries in models move to clinical trials in humans. However, a „bedside to bench to bedside“ approach may be more promising with respect to clinical relevance, since it starts with a clinical observation that can serve as a research paradigm to elucidate… Read more »

Fampridine and real-life walking in multiple sclerosis: Low predictive value of clinical test for habitual short-term changes.

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BACKGROUND: Fampridine improves walking speed in patients with multiple sclerosis (MS) in performance-based tests. The impact on habitual mobility and its correlation with clinical tests has not been analysed. OBJECTIVE: To investigate the association between clinical response criteria and habitual mobility in MS patients starting a fampridine treatment. METHODS: During a four-week baseline-to-treatment study, we… Read more »

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

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We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG,… Read more »

Plasticity of Th17 Cells in Autoimmune Kidney Diseases.

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The ability of CD4+ T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4+ T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the… Read more »

Development and Feasibility of an Evidence-Based Patient Education Program for Managing Fatigue in Multiple Sclerosis: The „Fatigue Management in MS“ Program (FatiMa)

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BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. Fatigue is a common and disabling symptom, often causing decreased quality of life, social withdrawal, and unemployment. We developed and studied the feasibility of a cognitive-behavioral group intervention to manage fatigue in MS. We aimed to integrate the concepts of… Read more »

Multiple Sclerosis: Molecular mimicry of an antimyelin HLA class I restricted T-cell receptor

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OBJECTIVE: To identify target antigens presented by human leukocyte antigen (HLA)-A*02:01 to the myelin-reactive human T-cell receptor (TCR) 2D1, which was originally isolated from a CD8+ T-cell clone recognizing proteolipid protein (PLP) in the context of HLA-A*03:01, we employed a new antigen search technology. METHODS: We used our recently developed antigen search technology that employs… Read more »

Heterogenity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging.

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PURPOSE: To assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC). MATERIALS AND METHODS: Seventeen MS-patients… Read more »

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

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INTRODUCTION: Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown… Read more »

Patient education programme on immunotherapy in multiple sclerosis (PEPIMS): A controlled rater-blinded study.

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OBJECTIVE: To investigate the effectiveness of a multi-component evidence-based education programme on disease modifying therapies in multiple sclerosis. DESIGN: Controlled trial with two consecutive patient cohorts and a gap of two months between cohorts. SETTING: Three neurological rehabilitation centres. SUBJECTS: Patients with multiple sclerosis within rehabilitation. INTERVENTIONS: Control group (CG) participants were recruited and received… Read more »

Steroid regulation of T cell function appears unaltered in borderline personality disorder.

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Borderline personality disorder (BPD) is characterized by instability of interpersonal relationships and affection, impulsivity, and cognitive disruptions. Increasing evidence suggests hypothalamic-pituitary-adrenal (HPA) axis alterations in BPD. Changed glucocorticoid sensitivity of peripheral blood mononuclear cells is known in mood and posttraumatic stress disorders, representing frequent comorbidities in BPD. However, to the authors‘ knowledge, in BPD glucocorticoid… Read more »

„History had taken such a large piece out of my life“ – Neuroscientist refugees from Hamburg during National Socialism.

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Approximately 9,000 physicians were uprooted for so-called „racial“ or „political“ reasons by the Nazi regime and 6,000 fled Germany. These refugees are often seen as survivors who contributed to a „brain drain“ from Germany. About 432 doctors (all specialties, private and academic) were dismissed from the major German city of Hamburg. Of these, 16 were… Read more »

Improved Lesion Detection by Using Axial T2-Weighted MRI with Full Spinal Cord Coverage in Multiple Sclerosis.

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MATERIALS AND METHODS: One hundred fifteen patients with definite or suspected MS underwent an MR imaging examination including 3-mm sagittal and 3.5-mm axial T2-weighted images with full spinal cord coverage. T2WI lesions were identified on axial and sagittal scans independently by 2 raters. Axial diameter, craniocaudal extension, lesion intensity, and location were analyzed. RESULTS: Four… Read more »

Sex effects on inflammatory and neurodegenerative processes in multiple sclerosis.

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Clinical observations in human autoimmune diseases such as multiple sclerosis (MS) suggest a pivotal role of sex-related factors in the etiopathogenesis. These include a female preponderance in MS incidence and an increasing sex bias over time, a parent-of-origin effect in MS inheritance, and the protective effect of pregnancy on disease activity. The complex interplay of… Read more »

Characterizing the phenotype of multiple sclerosis-associated depression in comparison with idiopathic major depression.

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BACKGROUND: Depression is a common co-morbidity in patients with multiple sclerosis (MS). While somatic symptoms of MS correlate with depression levels, it is unclear whether the clinical presentation of MS-associated depression differs from patients with „idiopathic“ major depressive disorder (MDD). OBJECTIVE: To compare the clinical phenotype of depression among MS and idiopathic MDD patients. METHODS:… Read more »

Quantitative T2* mapping reveals early temporo-spatial dynamics in an ischemic stroke model.

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BACKGROUND: Oxyhemoglobin-sensitive sequences, namely T2*, can indirectly depict changes in oxygen extraction. Purpose of this study was to investigate the dynamics of T2* changes in ischemic tissue. NEW METHOD: We investigated earliest temporo-spatial dynamics within ischemic tissue, measured with quantitative T2* imaging in the histologically defined infarct core and surrounding surviving tissue. Middle cerebral artery… Read more »

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

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BACKGROUND: Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. OBJECTIVE: We… Read more »

Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses.

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OBJECTIVE: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. METHODS: A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial… Read more »

Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array.

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Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array in a large German study. German MS cases (n = 4,476) and German controls (n = 5,714) were genotyped using the Illumina… Read more »

Distinct functionality of neutrophils in multiple sclerosis and neuromyelitis optica.

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BACKGROUND: In contrast to multiple sclerosis (MS), lesions in neuromyelitis optica (NMO) frequently contain neutrophils. However, the phenotypic profile of neutrophils in these two distinct pathologies remains unknown. OBJECTIVE: Our aim is to better understand the potential contribution of neutrophils to NMO and MS pathology. METHODS: We performed the first functional analysis of blood neutrophils… Read more »

Immune and neurotrophin stimulation by electroconvulsive therapy: is some inflammation needed after all?

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A low-grade inflammatory response is commonly seen in the peripheral blood of major depressive disorder (MDD) patients, especially those with refractory and chronic disease courses. However, electroconvulsive therapy (ECT), the most drastic intervention reserved for these patients, is closely associated with an enhanced haematogenous as well as neuroinflammatory immune response, as evidenced by both human… Read more »

Noise robust spatially regularized myelin water fraction mapping with the intrinsic B1 -error correction based on the linearized version of the extended phase graph model.

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PURPOSE: To improve the quantification accuracy of transverse relaxometry by accounting for B1 -error, after minimizing slice profile imperfections. MATERIALS AND METHODS: The slice profile of refocusing pulses was optimized by setting refocusing slice thicknesses three times that of the excitation pulse. The first step of data processing combined the L-curve approach with the linearized… Read more »

Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires.

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OBJECTIVE: Multiple sclerosis and major depressive disorder frequently co-occur but depression often remains undiagnosed in this population. Self-rated depression questionnaires are a good option where clinician-based standardized diagnostics are not feasible. However, there is a paucity of data on diagnostic accuracy of self-report measures for depression in multiple sclerosis (MS). Moreover, head-to-head comparisons of common… Read more »

Central Role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.

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OBJECTIVE: Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes.Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell… Read more »

Risk Knowledge in Relapsing Multiple Sclerosis (RIKNO 1.0) – Development of an Outcome Instrument for Educational Interventions.

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BACKGROUND: Adequate risk knowledge of patients is a prerequisite for shared decision making but few attempts have been made to develop assessment tools. Multiple Sclerosis (MS) is a chronic inflammatory disease of young adults with an increasing number of partially effective immunotherapies and therefore a paradigmatic disease to study patient involvement. OBJECTIVE/METHODS: Based on an… Read more »

Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: study protocol for a cluster randomised controlled trial.

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BACKGROUND: Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of… Read more »

Relapse in multiple sclerosis.

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Relapse of multiple sclerosis is a patient reported, or objectively observed, event typical of an acute inflammatory demyelinating event in the central nervous system, current or historical, with a duration of at least 24 hours. The differential diagnosis of a relapse includes alternative neurological diagnoses, pseudo-relapses, short lived paroxysmal symptoms, day to day fluctuations, and… Read more »

Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.

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PURPOSE: Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients. MATERIALS AND METHODS: Thirty-three… Read more »

Ecological validity of walking capacity tests in multiple sclerosis.

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BACKGROUND: Ecological validity implicates in how far clinical assessments refer to real life. Short clinical gait tests up to ten meters and 2- or 6-Minutes Walking Tests (2MWT/6MWT) are used as performance-based outcomes in Multiple Sclerosis (MS) studies and considered as moderately associated with real life mobility. OBJECTIVE: To investigate the ecological validity of 10… Read more »

Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging.

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PURPOSE: Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology. METHODS: Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values… Read more »

Patient expression of emotions and neurologist responses in first multiple sclerosis consultations.

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BACKGROUND: Anxiety and depression are common in people with multiple sclerosis (MS), but data on emotional communication during MS consultations are lacking. We assessed patient expressions of emotion and neurologist responses during first-ever MS consultations using the Verona Coding Definitions of Emotional Sequences (VR-CoDES). METHODS: We applied VR-CoDES to recordings/transcripts of 88 outpatient consultations (10… Read more »

Managing Neuropsychological Impairment in Multiple Sclerosis: Pilot Study on a Standardized Metacognitive Intervention.

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BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system of potential autoimmune origin that is frequently associated with psychological disorders and cognitive deficits, as well as with fatigue, stress, and psychosocial burden. These factors often cause decreased quality of life, social withdrawal, and unemployment. We describe the development of… Read more »

Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus.

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OBJECTIVE: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, leading to memory impairment in up to 65% of patients. Memory dysfunction in MS has been associated with loss of synapses in the hippocampus, but its molecular basis is unknown. Accumulating evidence suggests that components of the complement system, C1q and C3,… Read more »

Thalamic-hippocampal-prefrontal disruption in relapsing-remitting multiple sclerosis.

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BACKGROUND: Cortical, thalamic and hippocampal gray matter atrophy in relapsing-remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. OBJECTIVE: To assess MS damage to a hippocampal-thalamic-prefrontal network and the relative contributions of its components to specific cognitive… Read more »

Changes of Motivational Variables in Patients with Multiple Sclerosis in an Exercise Intervention: Associations between Physical Performance and Motivational Determinants.

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OBJECTIVES: This study examines the effects of a standardized fitness training on motivational factors such as the intention to be physically active, self-efficacy, perceived barriers, counterstrategies, and exercise specific social support in patients with progressive Multiple Sclerosis (MS) and the relation of these factors to physical performance. METHODS: Moderately disabled patients with secondary or primary… Read more »

An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial.

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BACKGROUND: With a lifetime risk for major depressive disorder of up to 50%, depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated. We investigated the potential of a fully automated, internet-based, cognitive behavioural therapy programme, Deprexis, to reduce depressive symptoms in patients with multiple sclerosis. METHODS: For this randomised controlled… Read more »

Stem cell transplantation for multiple sclerosis : Hamburg experiences and state of international research.

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BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is still not the standard treatment for highly inflammatory multiple sclerosis (MS). Even though randomized controlled trials are lacking, predictors for treatment response have been established. Since 2007, ten patients have received aHSCT in Hamburg. OBJECTIVE: To present observational data from patients treated in Hamburg and a review… Read more »

Immunopathology of multiple sclerosis.

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Two decades of clinical experience with immunomodulatory treatments for multiple sclerosis point to distinct immunological pathways that drive disease relapses and progression. In light of this, we discuss our current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still… Read more »

Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function.

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Recent association studies have linked numerous genetic variants with an increased risk for multiple sclerosis, although their functional relevance remains largely unknown. Here we investigated phenotypical and functional consequences of a genetic variant in the CD226 gene that, among other autoimmune diseases, predisposes to multiple sclerosis. Phenotypically, effector and regulatory CD4(+) memory T cells of… Read more »

Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.

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Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) is permeable to Na+ and Ca2+, and excessive accumulation of these ions is associated with axonal degeneration. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After… Read more »

Informed shared decision making about immunotherapy for patients with multiple sclerosis (ISDIMS): a randomized controlled trial.

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BACKGROUND AND PURPOSE: To evaluate the effects of an evidence-based patient decision aid (DA) on multiple sclerosis (MS) immunotherapy. METHODS: Two hundred and ninety-seven MS patients who were considering or reconsidering immunotherapy participated in a randomized community-based controlled trial in Germany. An intervention group (IG) received the DA and a control group (CG) received standard… Read more »

Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis.

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Recent findings in the animal model for multiple sclerosis (MS), experimental autoimmune encephalomyelitis, implicate a novel CD4+ T-cell subset (TH17), characterized by the secretion of interleukin-17 (IL-17), in disease pathogenesis. To elucidate its role in MS, brain tissues from patients with MS were compared to controls. We detected expression of IL-17 mRNA (by in situ… Read more »

Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis.

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The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4(+) T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8(+) T cells are controversial. We have generated humanized mice expressing the… Read more »

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes.

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AIMS/HYPOTHESIS: There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates… Read more »

Smaller cornu ammonis 2-3/dentate gyrus volumes and elevated cortisol in multiple sclerosis patients with depressive symptoms.

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BACKGROUND: The hippocampus is likely involved in mood disorders, but in vivo evidence for the role of anatomically distinct hippocampal subregions is lacking. Multiple sclerosis, an inflammatory disease of the central nervous system, is linked to a high prevalence of depression as well as hippocampal damage and may thus provide important insight into the pathologic… Read more »

TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.

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In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this… Read more »

Childhood trauma in multiple sclerosis: a case-control study.

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OBJECTIVE: To investigate the association between childhood trauma and multiple sclerosis (MS) by comparing histories of child abuse and neglect between patients with MS and adults from the general population in a cross-sectional case-control study. Previous research has demonstrated a connection between MS and a variety of emotional stressors, but childhood trauma, which is known… Read more »

Sex-related factors in multiple sclerosis susceptibility and progression.

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The pathogenesis of multiple sclerosis (MS) involves complex interactions between genetic susceptibility and environmental triggers. Clinical observations suggest that the study of sex differences might provide important insight into mechanisms of pathogenesis and progression of the disease in patients. MS occurs more frequently in women than in men, indicating that sex-related factors have an effect… Read more »

Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation.

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CONTEXT: Glucocorticoids (GC) are powerful endogenous and therapeutic modulators of inflammation and play a critical role for controlling autoimmunity. GC resistance can be seen in patients with cell-mediated autoimmune disorders, but it is unknown whether this represents a stable trait or a state. OBJECTIVE: The objective of the study was to determine whether GC resistance… Read more »

Long-term treatment risks in multiple sclerosis: risk knowledge and risk perception in a large cohort of mitoxantrone-treated patients.

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BACKGROUND: Balancing treatment benefits and risks is part of a shared decision-making process before initiating any treatment in multiple sclerosis (MS). Patients understand, appreciate and profit from evidence-based patient information (EBPI). While these processes are well known, long-term risk awareness and risk processing of patients has not been studied. Mitoxantrone treatment in MS is associated… Read more »

Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis.

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Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the CNS, and imposes major burdens on young lives. Great progress has been made in understanding and moderating the acute inflammatory components of MS, but the pathophysiological mechanisms of the concomitant neurodegeneration–which causes irreversible disability–are still not understood. Chronic inflammatory processes that continuously disturb… Read more »

Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

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BACKGROUND: New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS)–the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially… Read more »

CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis.

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Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) T cells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) T cells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which… Read more »

A 3meter Timed Tandem Walk is an early marker of motor and cerebellar impairment in fully ambulatory MS patients.

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BACKGROUND: Mobility assessment in Multiple Sclerosis (MS) is crucial for trials and individual patient counseling. Up to now, standard tests as the Timed 25-Foot Walk (T25FW) are restricted by floor effects in mildly disabled patients. The 3-meter Timed Tandem Walk (TTW) as a possibly more sensitive measure has not been investigated yet. OBJECTIVE: To investigate… Read more »

Regression to the Mean and Predictors of MRI Disease Activity in RRMS Placebo Cohorts – Is There a Place for Baseline-to-Treatment Studies in MS?

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BACKGROUND: Gadolinium-enhancing (GD+) lesions and T2 lesions are MRI outcomes for phase-2 treatment trials in relapsing-remitting Multiple Sclerosis (RRMS). Little is known about predictors of lesion development and regression-to-the-mean, which is an important aspect in early baseline-to-treatment trials. OBJECTIVES: To quantify regression-to-the-mean and identify predictors of MRI lesion development in placebo cohorts. METHODS: 21 Phase-2… Read more »

Detection of altered hippocampal morphology in multiple sclerosis-associated depression using automated surface mesh modeling.

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Depression is very common in multiple sclerosis (MS) but the underlying biological mechanisms are poorly understood. The hippocampus plays a key role in mood regulation and is implicated in the pathogenesis of depression. This study utilizes volumetric and shape analyses of the hippocampus to characterize neuroanatomical correlates of depression in MS. A cross-section of 109… Read more »

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

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BACKGROUND: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. OBJECTIVE: To investigate the potential of standardized exercise as a therapeutic… Read more »