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 »