Posts nach: jan broder engler

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 (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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

Keywords: Disease-modifying therapy; Multiple sclerosis; Patient perspective; Patient preference; Shared decision making

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 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 »

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 »

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 »

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 »

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 »

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 »

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 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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 (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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »

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 »