Elevated serum levels of soluble interleukin-2 receptor in patients with Wegener’s granulomatosis. Association with disease activity.

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OBJECTIVE: To investigate whether soluble interleukin-2 receptor (sIL-2R), a marker of T cell activation, could be a useful marker of disease activity in Wegener’s granulomatosis (WG). METHODS: Soluble IL-2R levels were determined by enzyme-linked immunosorbent assay. WG disease activity in 102 patients was assessed according to clinical features and levels of classic antineutrophil cytoplasmic antibody… Read more »

[Immunological abnormalities in migraine and cluster headache-epiphenomenon or pathogenetic factors?].

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An increasing number of papers deal with immunological factors in headache syndromes such as migraine and cluster headache. The aim of this review is to give an overview of the factors that have been measured and to assess their reliability and relevance for the pathogenesis of these headaches. Most of the studies are handicapped by… Read more »

[Intravascular lymphomatosis of the nervous system–case report and review of the literature].

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We report on a typical case of intravascular lymphomatosis, a rarely diagnosed, generalised intravascular lymphoma usually of the B-cell type. In most cases there is a lack of clear haematological findings but in more than 50% intravascular lymphomatosis presents with symptoms of the central nervous system. Every rapidly progressive neurological deficit, especially the association of… Read more »

Cerebral hyperperfusion injury after percutaneous transluminal angioplasty of extracranial arteries.

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Cerebral hyperperfusion syndrome after carotid endarterectomy (CEA) is a rare but well-known phenomenon. Percutaneous transluminal angioplasty (PTA) is being widely evaluated for treatment of selected stenoses of the extracranial arteries. Its benefits and risks still need to be established. Hyperperfusion injury (HI) after PTA of cerebral arteries has not been reported. We describe two patients… Read more »

FHL-1/reconectin and factor H: two human complement regulators which are encoded by the same gene are differently expressed and regulated.

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FHL-1/reconectin and factor H are two human complement regulators which are encoded by a single gene. FHL-1/reconectin contains the first 7 of 20 SCR protein domains of factor H and has four unique residues attached to its C-terminal end. The overlapping region of 445 amino acids explains the related complement regulatory functions of the two… Read more »

Interleukin-12 is detectable in sera of patients with multiple sclerosis – association with chronic progressive disease course?

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Multiple sclerosis (MS) is widely accepted as a systemic T- cell-mediated autoimmune disease with a T-helper type-1 (TH-1) profile of cytokine production. We addressed the question whether interleukin-12 (IL-12), as a central mediator of TH-1-cell activities, is detectable in sera of MS patients, and if there is any association with disease activity. We analysed 171… Read more »

Factor H and disease: a complement regulator affects vital body functions.

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Factor H is a multidomain and multifunctional protein. As a complement regulator factor H determines the fate of newly formed C3b and controls formation and stability of C3 convertases both in the fluid phase and on cell surfaces. In addition, this plasma protein displays functions outside complement control as it has been suggested to act… Read more »

Current status of multiple sclerosis therapy in Germany: a national survey.

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We conducted a semi-standardized enquiry concerning diagnostic, immunotherapeutic and supportive care strategies for multiple sclerosis (MS). A questionnaire was sent to all German neurological departments in December 1996, with 63% (n = 244) responding before May 1997. As might be expected, MS therapy in Germany is not very standardized. Most clinics use intravenous steroids for… Read more »

CD95-mediated apoptosis and DNA fragmentation in MS.

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OBJECTIVE: To investigate possible associations of soluble CD95 (sCD95) serum levels and DNA defragmentation with different MS disease stages and activities. METHODS: Sera of 114 patients were analysed by an ELISA technique for sCD95. In a subgroup of 18 relapsing-remitting MS patients and controls we studied DNA fragmentation by the TUNEL-method in CSF cytospins. RESULTS:… Read more »

Different regulation of factor H and FHL-1/reconectin by inflammatory mediators and expression of the two proteins in rheumatoid arthritis (RA).

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Factor H and the FHL-1/reconectin protein are two human plasma proteins that act as important regulators of the alternative complement pathway. Each protein is encoded by a unique transcript, but both mRNAs are derived from the factor H gene by means of alternative processing. In order to address potential functional differences between the two proteins… Read more »

Exceptional resistance of human H2 glioblastoma cells to complement-mediated killing by expression and utilization of factor H and factor H-like protein 1.

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Of over 20 nucleated cell lines we have examined to date, human H2 glioblastoma cells have turned out to be the most resistant to complement-mediated cytolysis in vitro. H2 cells expressed strongly the membrane attack complex inhibitor protectin (CD59), moderately CD46 (membrane cofactor protein) and CD55 (decay-accelerating factor), but no CD35 (complement receptor 1). When… Read more »

IL-1ra serum levels in disease stages of MS–a marker for progression?

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Interleukin-1 (IL-1) is one of the major proinflammatory cytokines expressed consistently in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1ra) is the only known naturally occurring specific antagonistic cytokine counteracting IL-1. Thus IL-1ra may have a downregulating potential in the disease course of MS. We analysed if circulating IL-1ra could be associated with different disease… Read more »

Failure of ondansetron in treating cerebellar tremor in MS patients–an open-label pilot study.

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Cerebellar tremor is a frequent and disabling symptom in multiple sclerosis (MS) patients. Supportive pharmacological treatment with different drugs showed only minor effects in a few studies and in clinical practice. Encouraged by previous studies with ondansetron, a 5HT3-antagonist, we conducted a small open-label, prospective and controlled study with 14 MS patients suffering predominantly from… Read more »

Disease specific quality of life instruments in multiple sclerosis: validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS).

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Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range… Read more »

Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H.

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Factor H (FH) is a potent suppressor of the alternative pathway of C in plasma and when bound to sialic acid- or glycosaminoglycan-rich surfaces. Of the three interaction sites on FH for C3b, one interacts with the C3d part of C3b. In this study, we generated recombinant constructs of FH and FH-related proteins (FHR) to… Read more »

Oral terbutaline differentially affects cytokine (IL-10, IL-12, TNF, IFNg) release in multiple sclerosis patients and controls.

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Administration of beta-receptor agonists alleviate experimental multiple sclerosis (MS) in animal models. In this study, we investigated the effects of terbutaline (5 mg) on IL-10, IL-12, IFN-gamma and TNF-alpha production in whole blood stimulation cultures. IL-10 and IL-12 production were significantly enhanced in controls but not in MS patients (p=0.03 and p=0.001). Effects were not… Read more »

Visual recovery in a man with the rare combination of mtDNA 11778 LHON mutation and a MS-like disease after mitoxantrone therapy.

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We describe a young man with prognostic unfavourable homoplasmatic mitochondrial DNA(mt DNA) 11778 Leber’s hereditary optic neuropathy (LHON) point mutation and confirmed multiple sclerosis (MS). This combination of LHON and MS-like disease is rare in both sexes, and in men has been described in only a few case reports. In a 4-year follow-up during immunosuppressive… Read more »

Prolactin stimulation in multiple sclerosis–an indicator of disease subtypes and activity?

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Prolactin (PRL) belongs to the growth and lactogenic hormone family and has potent immunomodulating properties. Mild hyperprolactinemia has been found to enhance several autoimmune diseases and increased PRL plasma levels have been described in the experimental multiple sclerosis (MS) model while the PRL antagonist bromocriptine was able to suppress the disease. As studies of PRL… Read more »

Endocrine and cytokine responses to acute psychological stress in multiple sclerosis.

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Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. An impaired hypothalamopituitary axis and stress reactivity have extensively been discussed without convincing experimental evidence. We choose a standardized acute psychological stressor to determine whether MS patients show altered endocrine and immune responses to stress. In 35 relapsing-remitting MS patients we found elevated… Read more »

Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis.

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Hypothalamo-pituitary-adrenal (HPA) dysregulation has recently been demonstrated in multiple sclerosis (MS) by means of combined dexamethasone corticotropin-releasing hormone (Dex-CRH) suppression tests. Authors found a correlation with course of disease and to a lesser extent with depressive symptoms. In this study, we aimed to further evaluate whether HPA disturbances in MS are correlated with cognitive impairment,… Read more »

MICA/NKG2D-mediated immunogene therapy of experimental gliomas.

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The failure of conventional cancer therapy renders glioblastoma an attractive target for immunotherapy. Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells. We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family… Read more »

Endocrine and cytokine responses to standardized physical stress in multiple sclerosis.

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Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine… Read more »

Cognitive impairment in multiple sclerosis does not affect reliability and validity of self-report health measures.

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Patient self-report health measures have received increasing recognition as supplementary outcome parameters in multiple sclerosis (MS). Given the high prevalence of cognitive problems in this population, reliability and validity of self-report instruments in patient groups with cognitive impairment is essential, especially when using such scales longitudinally. A sample of 80 MS patients with cognitive dysfunction… Read more »

Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.

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Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both… Read more »

Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls.

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Neurotrophins like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to play an important role in neuronal repair and plasticity. Recent experimental evidence suggests neuroprotective effects of these proteins in multiple sclerosis (MS). We investigated the response of serum NGF and BDNF concentrations to standardized acute exercise in MS patients and controls…. Read more »

Delivering the diagnosis of MS–results of a survey among patients and neurologists.

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OBJECTIVES: The need for an early disclosure of the diagnosis of multiple sclerosis (MS) has become more pressing with the publication of two recent randomized trials which have indicated that very early treatment may favourably alter the disease course. We assessed the current status of diagnostic and therapeutic information on MS from the point of… Read more »

Stronger endocrine responses after brief psychological stress in women at familial risk of breast cancer.

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Recent research has linked exposure to chronic stress to altered acute stress responses and suggests a sensitizing effect of chronic stress leading to a stronger endocrine and cardiovascular response to acute stressors. Substantial evidence indicates that familial breast cancer risk is a chronic life stressor with higher levels of self reported distress. In this study,… Read more »

Effects of mitoxantrone on multiple sclerosis patients‘ lymphocyte subpopulations and production of immunoglobulin, TNF-alpha and IL-10.

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We designed this longitudinal study to clarify the short- and long-term effects of mitoxantrone on the immune system in a subgroup of multiple sclerosis patients treated at our centre. After 14 days we found a highly significant sustained reduction of leucocytes, primarily affecting neutrophils and most lymphocyte subsets except for naive and activated T lymphocytes…. Read more »

Collateral circulation is an independent radiological predictor of outcome after thrombolysis in acute ischaemic stroke.

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We tested the hypothesis that the type of vascular occlusion, recanalisation and collateralisation are predictive of outcome after thrombolytic therapy in acute ischaemic stroke. We carried out angiography and local intra-arterial (97) or systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic stroke in the territory of the internal carotid… Read more »

Escalating immunotherapy of multiple sclerosis–new aspects and practical application.

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Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data… Read more »

The innate immune response in the central nervous system and its role in glioma immune surveillance.

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The innate immune system encompasses natural killer (NK) cells, macrophages and granulocytes, the complement system and antimicrobial peptides. Recognition pathways of the innate immune system include microbial non-self recognition, missing-self recognition and induced- self recognition. The central nervous system (CNS) participates in responses of the innate immune system. However, immune inhibitory and anti-inflammatory mechanisms physiologically… Read more »

Decisional role preferences, risk knowledge and information interests in patients with multiple sclerosis.

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OBJECTIVE: Shared decision making is increasingly recognized as the ideal model of patient-physician communication especially in chronic diseases with partially effective treatments as multiple sclerosis (MS). To evaluate prerequisite factors for this kind of decision making we studied patients‘ decisional role preferences in medical decision making, knowledge on risks, information interests and the relations between… Read more »

RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo.

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Transforming growth factor (TGF)-beta is the key molecule implicated in impaired immune function in human patients with malignant gliomas. Here we report that patients with glioblastoma, the most common and lethal type of human glioma, show decreased expression of the activating immunoreceptor NKG2D in CD8(+) T and natural killer (NK) cells. TGF-beta is responsible for… Read more »

[Development and validation of assessment instruments for shared decision making].

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The German Ministry for Health and Social Security is funding ten projects to introduce shared decision making into clinical practice. The medical problems the projects are focussing on were chosen from among various diseases (e. g. depression, multiple sclerosis, cancer). The ten projects achieved consensus on a core set of instruments for the measurement of… Read more »

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis.

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In recent years it has become clear that multiple sclerosis (MS) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects. We studied immunological, endocrine and neurotrophic factors as well as coordinative function and quality of life during an… Read more »

Higher Beck depression scores predict delayed epinephrine recovery after acute psychological stress independent of baseline levels of stress and mood.

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Depressive symptoms in the non-clinical range have been linked to increased health risks. Recent theorizing raises the possibility that heightened physiologic responses to acute stress and/or slowed stress recovery in individuals with depressive symptoms may contribute to increased risk. We investigated stress-induced catecholamine responses and recovery patterns using a modified version of the Trier Social… Read more »

Steroid treatment for relapses in multiple sclerosis – the evidence urges shared decision-making.

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OBJECTIVES: Therapy of acute relapses in multiple sclerosis with corticosteroids (CC) remains uncertain with respect to route, dosage and effectiveness. This makes the treatment of relapses a clinical field where ’shared decision-making (SDM)‘ could be of advantage for the patients. A prerequisite for SDM is the provision of evidence-based information for the patients. The British… Read more »

A patient questionnaire for radiation-induced brachial plexopathy.

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We analyzed the usefulness of a symptom questionnaire to screen for radiation-induced brachial plexopathy (RIBP) after breast cancer treatment. Four questions addressed distal and proximal paresis: impaired hand functions, problems raising the arm, carrying weights, and lifting objects from a high shelf. Eighty-one relapse-free patients were neurologically examined. Treatment was mastectomy (51%) or breast-conserving surgery… Read more »

[The concept of allostasis and allostatic load: psychoneuroimmunological findings].

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Classical theories have conceptualized stress as a reaction to threat to the homeostasis within the organism requiring an adaptive response. However, postulating mechanisms that could link such responses to long-term detrimental health outcomes remains difficult. The allostatic load concept enables us to think about how mediators can be protective in the short run but may… Read more »

The role of stress-response systems for the pathogenesis and progression of MS.

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Disease progression in multiple sclerosis (MS)–an inflammatory demyelinating and neurodegenerative disease with a presumed T-cell driven autoimmune origin–has long been hypothesized to be associated with stress. However, this notion has only recently been supported by prospective clinical studies. Several clinical and molecular studies in MS and its animal models have recently shown disruptions in the… Read more »

[Criteria for evidence-based patient information].

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Evidence-based patient information (EBPI) is a prerequisite for informed patient choice. However, there is as yet no discussion as to what can be expected of EBPI. The present paper provides an overview of the criteria presently used or discussed for the development of EBPI. Ethics guidelines demand that EBPI are offered and made available to… Read more »

[Effects of exercise in chronically ill patients. Examples from oncology and neurology].

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Epidemiologic studies increasingly have demonstrated a correlation between physical inactivity and certain chronic diseases. Already in the 1970s exercise programs for cardiovascular patients were established, whereas in other severe chronic illnesses such as breast cancer or multiple sclerosis exposure to physical stress seemed to be a contraindication. Today there is a grow ing body of… Read more »

HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo.

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The nonclassical MHC class I molecule HLA-E is the only known ligand for CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta T cells. HLA-E may transmit either activating signals via CD94/NKG2C or inhibitory signals mediated by CD94/NKG2A. Here we show that HLA-E is expressed at mRNA and protein level in human long-term… Read more »

Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?

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Multiple sclerosis afflicts more than 1 million individuals worldwide and is widely considered to be an autoimmune disease. Traditionally, CD4(+) T helper cells have almost exclusively been held responsible for its immunopathogenesis, partly because certain MHC class II alleles clearly predispose for developing multiple sclerosis and also, because of their importance in inducing experimental autoimmune… Read more »

Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study.

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We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to… Read more »

Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis.

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Clinical studies have shown that groups of multiple sclerosis (MS) patients exhibit a chronically activated hypothalamo-pituitary-adrenal (HPA) axis. However, the association of HPA axis activity and disease progression in MS is unknown. In this longitudinal study over a 3-year follow-up period, we report that patients who exhibited stronger HPA reactivity at baseline were significantly more… Read more »

Hypertension and hypothalamo-pituitary-adrenal axis hyperactivity affect frontal lobe integrity.

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Chronically elevated cortisol levels have been associated with elevated blood pressure, brain atrophy, and cognitive impairments. In this cross-sectional exploratory study, we assessed whether hypertension was related to hypothalamo-pituitary-adrenal axis hyperactivity and whether this may in part explain prefrontal brain atrophy and cognitive impairments in this population. We studied 27 patients with hypertension and 27… Read more »

Altered cytokine responses to cognitive stress in multiple sclerosis patients with fatigue.

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This study intended to examine if the immune response to a cognitive task as a variant of psychological stress in MS patients is distinct from healthy controls. The experiment was part of a larger study on mechanisms and measurements of MS fatigue. Patients (n =23) and controls (n =25) participated in a cognitive task lasting… Read more »

Multiple sclerosis: MHC associations and therapeutic implications.

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Multiple sclerosis (MS) is an autoimmune disease with an important genetic component. The strongest genetic association is with the major histocompatibility complex (MHC) region. Several MHC alleles predispose to the disease, the most prominent of which are certain alleles in the HLA-DR2 haplotype. Functional and structural studies have helped to explain the molecular basis of… Read more »

Stress and disease progression in multiple sclerosis and its animal models.

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Since the first description of multiple sclerosis (MS) by Charcot, stress has been hypothesized to be a potential trigger of relapses. In recent years, data from observational studies in MS patients have provided some support for an association between stress and MS relapses. Furthermore, studies employing the MS animal model experimental autoimmune encephalomyelitis have shown… Read more »

Humanized mouse models for organ-specific autoimmune diseases.

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Murine models for human autoimmune diseases are an essential tool for studying pathogenesis and for identifying new therapeutic targets. Mice are not the natural disease host, and conventional models have proved to be poor predictors of efficacy and safety in recent trials aiming to translate drug and biologic treatments to humans. Evidently, further steps towards… Read more »

Patient information on cognitive symptoms in multiple sclerosis – acceptability in relation to disease duration.

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OBJECTIVE: Recently, regular cognitive screening assessments have been advised in multiple sclerosis (MS). No studies have been carried out yet on the acceptability of information on cognitive deficits among MS patients. MATERIALS AND METHODS: Translation of an information booklet developed by a working group of European MS Rehabilitation Centers. Distribution of the booklet among 133… Read more »

TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells.

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NKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They transmit danger signals to NKG2D-expressing immune cells, leading to lysis of NKG2DL-expressing cells. We here report that the NKG2DL MHC class I-chain-related molecules A and B (MICA/B) and UL16-binding proteins (ULBP) 1-3 are expressed in human brain tumours in vivo, while expression levels are… Read more »

Depression and immunity: inflammation and depressive symptoms in multiple sclerosis.

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There is strong evidence that depression involves alterations in multiple aspects of immunity that may contribute to the development or exacerbation of a number of medical disorders and also may play a role in the pathophysiology of depressive symptoms. Accordingly, aggressive management of depressive disorders in medically ill populations or individuals at risk for disease… Read more »

Testosterone replacement therapy for the treatment of neurological and neuropsychiatric disorders.

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There is an accumulating body of evidence in the literature suggesting that testosterone may be neuroprotective and therefore have therapeutic value in the treatment of neurodegenerative diseases. In this article, the potential mechanisms of action of testosterone on the central nervous system are discussed, as well as the current evidence supporting the effect of testosterone… Read more »

The value of animal models for drug development in multiple sclerosis.

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The rodent model for multiple sclerosis, experimental allergic (autoimmune) encephalomyelitis (EAE), has been used to dissect molecular mechanisms of the autoimmune inflammatory response, and hence to devise and test new therapies for multiple sclerosis. Clearly, artificial immunization against myelin may not necessarily reproduce all the pathogenetic mechanisms operating in the human disease, but most therapies… Read more »

Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment.

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Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting young adults and leading to considerable disability. For many years, patients have been advised to avoid physical activity. Today, however, an increasing number of studies have shown beneficial effects of exercise training in MS. It has been reported that such programs not only improve fitness… Read more »

Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?

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BACKGROUND: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. METHODS: We compared whole blood stimulatory capacity for pro- (TNFalpha,… Read more »

Immune stimulatory effects of CD70 override CD70-mediated immune cell apoptosis in rodent glioma models and confer long-lasting antiglioma immunity in vivo.

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CD70 (CD27 ligand) promotes the expansion of primed lymphocytes by enhancing cell survival. Surprisingly, we previously observed that CD70 aberrantly expressed on human glioma cells promoted immune cell apoptosis and inhibited alloreactive lysis. Here we report that ectopic expression of CD70 in mouse glioma cells enhances apoptosis of T, B and NK cells in coculture,… Read more »

Evidence-based patient information about treatment of multiple sclerosis–a phase one study on comprehension and emotional responses.

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OBJECTIVE: This study analysis the comprehension and emotional responses of people suffering from multiple sclerosis when provided with an evidence-based information module. It is a core module of a comprehensive decision aid about immunotherapy. The core module is designed to enable patients to process scientific uncertainty without adverse effects. It considers existing standards for risk… Read more »

[Effects of a shared decision making model in psychiatric and neurologic practice].

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Involving patients in medical decisions is increasingly being advocated in medical fields other than psychiatry and neurology. A model of shared decision making might prove to be an ideal way of bridging the gap between patient-centred and evidence-based medicine. This report provides a survey of this shared decision making model and a discussion of its… Read more »

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

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

Participation preferences of patients with acute and chronic conditions.

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BACKGROUND: There is little knowledge as to whether the chronicity of a disease affects patients‘ desire for participation. AIM: To study whether participation preferences vary according to the type of disease. DESIGN, PARTICIPANTS AND METHODS: Data of 1,393 patients from six trials with different medical conditions (hypertension, depression, breast cancer, schizophrenia, multiple sclerosis, minor traumas)… Read more »

Long-term follow-up of cerebral aneurysms after endovascular therapy prediction and outcome of retreatment.

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BACKGROUND AND PURPOSE: The purpose of this study was to analyze angiographic and clinical results before and after additional endovascular therapy in patients with previously coiled but reopened cerebral aneurysms and to identify possible risk factors for retreatment of an aneurysm. MATERIALS AND METHODS: Follow-up with selective digital subtraction angiography was performed in 323/596 (54.2%)… Read more »

Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.

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In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and… Read more »

Stress and hypothalamic-pituitary-adrenal axis function in experimental autoimmune encephalomyelitis and multiple sclerosis – a review.

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Multiple sclerosis (MS) is an inflammatory and degenerative disease of the CNS with an assumed autoimmune-mediated pathogenesis. Stressful life events have been hypothesized as potential triggers of disease exacerbation. Animal studies using experimental autoimmune encephalomyelitis (EAE), as a model for MS, suggest that decreased hypothalamic-pituitary-adrenal (HPA) function may play a role in the increased susceptibility… Read more »

Shared decision making and self-management in multiple sclerosis–a consequence of evidence.

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Shared decision making is increasingly recognised as the ideal model of patient-physician communication especially in chronic diseases with partially effective treatments such as multiple sclerosis (MS). Since 2001, we studied prerequisites for patient participation in decision making as well as the effects of evidence-based patient information on decision making processes in MS. In pre-studies we… Read more »

Stress regulation in multiple sclerosis: current issues and concepts.

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Since its first description by Charcot, psychological stress has been considered a triggering factor for exacerbations in multiple sclerosis, but until recently the clinical evidence for a causal relation was weak. Over the past years, a growing number of studies have started to elucidate this association and highlight potential mechanisms, including brain-immune communication. On 5… Read more »

Informed shared decision making in multiple sclerosis–inevitable or impossible?

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Patients and health authorities increasingly claim active roles in health care decision making processes. As immune therapies in MS are partially effective MS is a prototypic condition for a shared decision making process. The treatment of acute relapses and the initiation, change or withdrawal of so called disease-modifying treatments are key decisions in MS management…. Read more »

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

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

[Visual rating of T2′-blood-oxygen-level-dependent magnetic resonance imaging in acute stroke patients–a pilot study].

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PURPOSE: Delineation of brain tissue that is at risk but not yet infarcted (penumbra) continues to be a major challenge for stroke imaging. Metabolic characterization of the penumbra might be able to be achieved using blood-oxygen-level-dependent (BOLD) imaging. MATERIALS AND METHODS: We analyzed MRI data from 20 patients within the first 6 hours after stroke… Read more »

Hypercholesterolemia in Asperger syndrome: independence from lifestyle, obsessive-compulsive behavior, and social anxiety.

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We report on elevated total cholesterol and low-density lipoprotein (LDL) levels in 22 individuals with Asperger syndrome compared with well-matched controls, after accounting for lifestyle variables and clinical symptomatology that could affect them. A potential role for dyslipidemia in the pathogenesis of some forms of autism is discussed.

Stem cell transplantation in multiple sclerosis.

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Following promising results in animal studies showing that immunosuppression and consecutive allogeneic bone marrow transplantation has the potential to significantly reduce autoimmunity, emerging data is supporting a benefit in patients with multiple sclerosis (MS) and other autoimmune disorders not responding to approved therapies. Until today, results on over 400 cases have been reported by the… Read more »

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

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

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

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

T2 relaxation time correlates of face recognition deficits in temporal lobe epilepsy.

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This study explored structural correlates of immediate and delayed face recognition in 22 nonsurgical patients with nonlesional, unilateral mesial temporal lobe epilepsy (TLE, 10 left/12 right). We measured T2 relaxation time bilaterally in the hippocampus, the amygdala, and the fusiform gyrus. Apart from raised T2 values in the ipsilateral hippocampus, we found increased T2 values… Read more »

Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone.

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BACKGROUND: Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that… Read more »

T2′ imaging predicts infarct growth beyond the acute diffusion-weighted imaging lesion in acute stroke.

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PURPOSE: To show that measurement of the transverse relaxation time that characterizes signal loss caused by local susceptibilities (T2′) is sensitive to an increased deoxyhemoglobin concentration in the brain, indicating tissue at risk for infarction. MATERIALS AND METHODS: The study was approved by the local institutional review board; patients or their guardians provided informed consent…. Read more »

Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable.

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Multiple sclerosis is a heterogeneous disease with varying clinical picture. There have been substantial efforts to develop outcome measurements for therapeutic interventions but very few studies have addressed the value of bodily functions from the patient perspective. In a randomly selected cohort of early (<5 years, n=84) and longer lasting disease courses (>15 years, n=82)… Read more »

Early anisotropy changes in the corpus callosum of patients with optic neuritis.

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INTRODUCTION: Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. METHODS: A total of 24 patients… Read more »

Clinical and tissue response to intravenous thrombolysis in tandem internal carotid artery/middle cerebral artery occlusion: an MRI study.

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BACKGROUND AND PURPOSE: The benefit of intravenous thrombolysis in tandem internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion remains unclear. We studied clinical and imaging outcome of intravenous thrombolysis in MRI-selected patients with tandem ICA/MCA occlusion as compared to isolated MCA occlusion. METHODS: We analyzed data of MRI-selected acute ischemic stroke patients treated with intravenous… Read more »

Age-dependent normal values of T2* and T2′ in brain parenchyma.

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BACKGROUND AND PURPOSE: Physiologic age-related T2* and T2′ values are required as reference for comparison with disease-related deviations. In our study, T2* and T2′ values (T2 values as control) were determined with MR imaging in healthy subjects to determine standard values and investigate age-related changes. MATERIALS AND METHODS: Data of 50 patients without intraparenchymal pathology… Read more »

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

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

Thrombolysis targeting MRI defined tissue at risk in minor stroke.

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BACKGROUND: Treatment with intravenous tissue plasminogen activator (IV-tPA) is usually not recommended in patients with minor stroke. Clinical and imaging outcome were studied after IV-tPA treatment based on MRI criteria in patients with minor stroke. METHODS: Data were analysed retrospectively of acute ischaemic stroke patients with minor stroke (National Institutes of Health Stroke Scale (NIHSS)… Read more »

Pathogenic CD8(+) T cells in multiple sclerosis.

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Traditionally, autoimmune pathogeneses have been attributed to CD4(+) T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens… Read more »

Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha).

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Matrix metalloproteinases (MMPs) have a crucial function in migration of inflammatory cells into the central nervous system (CNS). Levels of MMP-9 are elevated in multiple sclerosis (MS) and predict the occurrence of new active lesions on magnetic resonance imaging (MRI). This translational study aims to determine whether in vivo treatment with the pregnancy hormone estriol… Read more »

Estrogen and testosterone therapies in multiple sclerosis.

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It has been known for decades that females are more susceptible than men to inflammatory autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis, and psoriasis. In addition, female patients with these diseases experience clinical improvements during pregnancy with a temporary „rebound“ exacerbation postpartum. These clinical observations indicate an effect of sex hormones on disease and… Read more »

Suspected multiple sclerosis – what to do? Evaluation of a patient information leaflet.

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BACKGROUND: Parallel to the establishment of early treatments in multiple sclerosis (MS), new diagnostic criteria have made an earlier diagnosis possible. While there is ongoing discussion about possible benign courses and only partial effective treatments, there have been no attempts today to facilitate shared decision making on diagnostic testing between patients with suspected MS and… Read more »

Negative fluid-attenuated inversion recovery imaging identifies acute ischemic stroke at 3 hours or less.

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OBJECTIVE: To evaluate the use of fluid-attenuated inversion recovery (FLAIR) imaging as surrogate marker of lesion age within the first 6 hours of ischemic stroke. METHODS: e analyzed FLAIR and diffusion-weighted imaging (DWI) sequences performed within 6 hours of symptom onset in 120 consecutive patients with ischemic stroke with known symptom onset. The visibility of… Read more »

Estrogen treatment in multiple sclerosis.

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Currently available treatments for multiple sclerosis (MS) reduce inflammatory lesions on MRI and decrease clinical relapses but have limited effects on disability. Novel treatment options that target both the inflammatory as well as the neurodegenerative component of the disease are therefore needed. A growing body of evidence from basic science and clinical studies supports the… Read more »

Combination of T2*W and FLAIR abnormalities for the prediction of parenchymal hematoma following thrombolytic therapy in 100 stroke patients.

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INTRODUCTION: The objective of our study was to determine whether the combination of hypointense spots („cerebral microbleeds,“ CMBs) with a leukoaraiosis is associated with the risk of parenchymal hematoma (PH) after thrombolytic therapy. PATIENTS AND METHODS: We analyzed magnetic resonance imaging (MRI) scans acquired within 6 hours after symptom onset from 100 ischemic stroke patients…. Read more »

T2′ imaging indicates decreased tissue metabolism in frontal white matter of MS patients.

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BACKGROUND AND PURPOSE: T2′-Magnetic resonance imaging (MRI) allows estimation of oxygen metabolism in normal appearing white and gray matter (NAWM and NAGM) and is sensitive to local iron deposition. We hypothesized that T2′ imaging is feasible in routine use and reveals differences between MS patients and healthy subjects. METHODS: T2- and T2*-weighted images were acquired… Read more »

From genes to function: the next challenge to understanding multiple sclerosis.

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Susceptibility to multiple sclerosis is jointly determined by genetic and environmental factors, and progress has been made in defining some of these genetic associations, as well as their possible interactions with the environment. However, definitive proof for the involvement of specific genetic determinants in the disease will only come from studies that examine their functional… Read more »

Depression and immunity: inflammation and depressive symptoms in multiple sclerosis.

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An increasing body of evidence suggests that patients who have major depressive disorder show alterations in immunologic markers including increases in proinflammatory cytokine activity and inflammation. Inflammation of the central nervous system is a pathologic hallmark of multiple sclerosis (MS). Patients affected by this disease also show a high incidence of depression. Accumulating evidence from… Read more »

Modafinil effects in multiple sclerosis patients with fatigue.

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BACKGROUND: To investigate the effects of Modafinil on focused attention, motor function and motor excitability in patients with multiple sclerosis (MS) and fatigue. METHODS: 21 MS patients with fatigue were enrolled in this double-blind placebo-controlled study. Modafinil (MOD) or placebo (PL) was administered for 8 weeks. The d2 alertness test, the Nine Hole Peg Test… Read more »

Quantitative t2 values predict time from symptom onset in acute stroke patients.

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BACKGROUND AND PURPOSE: We hypothesize that in comparison to diffusion-weighted imaging, quantitative T2 values (qT2) are more directly related to water uptake in ischemic tissue, depending on time from symptom onset. We measured the increase of qT2 in the infarct core to quantify the correlation between time from symptom onset and change in qT2. METHODS:… Read more »

T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.

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Environmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a microbial peptide, common to several major classes of… Read more »

Abciximab is a safe rescue therapy in thromboembolic events complicating cerebral aneurysm coil embolization: single center experience in 42 cases and review of the literature.

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BACKGROUND AND PURPOSE: The purpose of this study was to estimate the safety and efficacy of abciximab treatment in combination with prophylactic heparin, acetylsalicylic acid (ASA), and clopidogrel application in cases of thrombus formation complicating endovascular coil embolization in cerebral aneurysms. METHODS: Thromboembolic incidents during endovascular management of 515 consecutive cerebral aneurysms were observed in… Read more »

[Evidence-based patient information: the example of immunotherapy for patients with multiple sclerosis].

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The article elucidates consideration of scientific criteria for the development and design of evidence-based patient information (EBPI). Immunotherapy of multiple sclerosis serves as an example. Since in EBPI lack of evidence or ambiguities in available evidence are explicitly communicated, processing of EBPI does not necessarily lead to certainty about benefit and harms of medical interventions…. Read more »

Patient education program to enhance decision autonomy in multiple sclerosis relapse management: a randomized-controlled trial.

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BACKGROUND: Contrary to strong recommendations for high-dose intravenous corticosteroid treatment for relapses in multiple sclerosis (MS), uncertainty remains about most aspects of relapse management. Oral corticosteroids administered by physicians or patients themselves or no corticosteroids also appear justifiable. OBJECTIVE: To evaluate an education program that aims to involve patients with MS in decisions on relapse… Read more »

Risk perception in natalizumab-treated multiple sclerosis patients and their neurologists.

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BACKGROUND: Natalizumab is associated with the potentially life-threatening side-effect progressive multifocal leukoencephalopathy (PML). Little is known about patients‘ and physicians‘ risk estimates and attitudes towards natalizumab treatment. METHODS: Consecutive natalizumab-treated patients (n = 69) and neurologists (n = 66) in two centres and cooperating private practices received an evidence-based three-page information leaflet about natalizumab-associated PML… Read more »

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

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

Correlates of cognitive dysfunction in multiple sclerosis.

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Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflammation, neurodegeneration, and neuroendocrine dysregulation. However, these different systems have never been studied in parallel and… Read more »

N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.

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Antibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid,… Read more »

Responsiveness of patient-based and external rating scales in multiple sclerosis: head-to-head comparison in three clinical settings.

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BACKGROUND: Patient-based rating scales and especially quality of life scales have received increasing attention as secondary outcome measures in multiple sclerosis (MS). Responsiveness to health-related change of quality of life scales is thus an important property when these measures are to be used successfully in clinical trials. METHODS: We conducted an analysis of 3 cohorts… Read more »

Why not? – Communicating stochastic information by use of unsorted frequency pictograms – a randomised controlled trial.

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OBJECTIVE: Statistical health risk information has been proven confusing and difficult to understand. While existing research indicates that presenting risk information in frequency formats is superior to relative risk and probability formats, the optimal design of frequency formats is still unclear. The aim of this study was to compare presentation of multi-figure pictographs in consecutive… Read more »

Patients‘ and observers‘ perceptions of involvement differ. Validation study on inter-relating measures for shared decision making.

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OBJECTIVE: Patient involvement into medical decisions as conceived in the shared decision making method (SDM) is essential in evidence based medicine. However, it is not conclusively evident how best to define, realize and evaluate involvement to enable patients making informed choices. We aimed at investigating the ability of four measures to indicate patient involvement. While… Read more »

Biological outcome measurements for behavioral interventions in multiple sclerosis.

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Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms… Read more »

Macromolecule content influences proton diffusibility in gliomas.

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OBJECTIVES: Different compositions of the extra cellular matrix with changing concentrations of more or less hydrophilic components like proteins may have a major influence on the diffusion phenomena found in gliomas. METHODS: 24 patients (14 male / 10 female) with histologically confirmed non necrotic glioma underwent preoperative MRI, including magnetisation transfer (MTR), triple echo T2… Read more »

Oral fingolimod (FTY720) in relapsing multiple sclerosis: impact on health-related quality of life in a phase II study.

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BACKGROUND: Health-related quality of life (HRQoL) worsens with multiple sclerosis (MS) relapses and disease progression. Common symptoms including depression and fatigue may contribute to poor HRQoL. OBJECTIVES: To report exploratory analyses assessing the impact of fingolimod (FTY720) on HRQoL and depression in a phase II study of relapsing MS. METHODS: The Hamburg Quality of Life… Read more »

Infarction of ’non-core-non-penumbral‘ tissue after stroke: multivariate modelling of clinical impact.

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There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of ’non-core-non-penumbral‘ (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established… Read more »

HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis.

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OBJECTIVE: To reassess the effect of modafinil, a wakefulness-promoting artificial psychostimulant, on fatigue and neuropsychological measures in patients with multiple sclerosis. METHODS: Multiple sclerosis (MS) patients with a baseline score of ≥4 on the Fatigue Severity Scale (FSS) and an Expanded Disability Status Scale score <7 were eligible for the 8-week randomized, double-blind, placebo-controlled study…. Read more »

Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis.

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The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of… Read more »

Predicting infarction within the diffusion-weighted imaging lesion: does the mean transit time have added value?

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BACKGROUND AND PURPOSE: There is ample evidence that in anterior circulation stroke, the diffusion-weighted imaging (DWI) lesion may escape infarction and thus is not a reliable infarct predictor. In this study, we assessed the predictive value of the mean transit time (MTT) for final infarction within the DWI lesion, first in patients scanned back-to-back with… Read more »

Multiple enlarged nerves on neurosonography: an unusual paraneoplastic case.

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Multiple nerve enlargements at non-entrapment sites are usually caused by hereditary or acquired immune-mediated neuropathies.We describe a case of multifocal hypertrophic mononeuropathies detected by nerve sonography with a clinical picture of progressive mononeuritis multiplex caused by a paraneoplastic syndrome associated with anti-Hu antibodies. This case illustrates an unusual but important paraneoplastic differential diagnosis of progressive… Read more »

[Autoimmune synaptic encephalopathies].

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Antibody-associated limbic encephalitis was usually seen as a paraneoplastic syndrome where the antibodies would target intracellular proteins. However, recent reports challenged this idea and described antibodies that target synaptic proteins expressed on the cell surface. These antibodies are not necessarily linked to tumors and should be regarded as a distinct entity of different autoimmune diseases…. Read more »

Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression.

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OBJECTIVE: Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity in depression and fatigue were examined in patients with relapsing-remitting MS (RRMS)…. Read more »

IL-21 and IL-21 receptor expression in lymphocytes and neurons in multiple sclerosis brain.

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IL-17-producing CD4(+) T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17-polarizing conditions (IL-6 and transforming growth factor-β). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression… Read more »

Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model.

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Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the acid-sensing ion channel 1 which, when activated under the acidotic tissue… Read more »

Accuracy of diagnostic tests in multiple sclerosis–a systematic review.

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New diagnostic criteria for multiple sclerosis (MS) have been recently proposed and further updates are upcoming. This systematic literature review summarizes diagnostic studies in suspected MS to clarify the value of diagnostic tests. We included studies of at least 40 patients followed up for 2 years. All studies are limited by the fact that no… Read more »

Signal intensity in T2′ magnetic resonance imaging is related to brain glioma grade.

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OBJECTIVES: T2′ values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2′ imaging to display regions with high metabolic activity in brain gliomas. METHODS: MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences…. Read more »

Decisions on multiple sclerosis immunotherapy: new treatment complexities urge patient engagement.

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For patients with multiple sclerosis (MS) involvement in treatment decisions becomes ever more imperative. Recently new therapeutic options have become available for the treatment of MS and more will be licensed in the near future. Although more efficacious and easier to administer, the new drugs pose increased risks of severe side effects. Also, new diagnostic… Read more »

Placebo cohorts in phase-3 MS treatment trials – predictors for on-trial disease activity 1990-2010 based on a meta-analysis and individual case data.

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BACKGROUND: Annualized relapse rates (ARR) in the placebo cohorts of phase-3 randomized controlled trials (RCT) of new treatments for relapsing remitting multiple sclerosis (RRMS) have decreased substantially during the last two decades. The causes of these changes are not clear. We consider a better understanding of this phenomenon essential for valuing the effects of new… Read more »

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

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

[Depression and neurological diseases].

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In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous… Read more »

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.

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Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number… Read more »

Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.

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The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced… Read more »

A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis.

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OBJECTIVE: Based on findings in animal models of autoimmune optic nerve inflammation, we have assessed the safety and efficacy of erythropoietin in patients presenting with a first episode of optic neuritis. METHODS: Patients with optic neuritis who attended the University Hospitals of Homburg/Saar, Göttingen, or Hamburg (Germany) were included in this double-blind, placebo-controlled, phase 2… Read more »

Completing the third person’s perspective on patients‘ involvement in medical decision-making: approaching the full picture.

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OBJECTIVE: Shared decision making is based on the idea of cooperation and partnership between patients and doctors. In this concept both parties may initiate and perform specific decision-making steps. However, the common observation-based instruments focus solely on doctors‘ behaviour. Content and quality of information provided to involve patients in medical decisions are hardly considered in… Read more »

Applying the theory of planned behaviour to multiple sclerosis patients‘ decisions on disease modifying therapy–questionnaire concept and validation.

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BACKGROUND: Patients making important medical decisions need to evaluate complex information in the light of their own beliefs, attitudes and priorities. The process can be considered in terms of the theory of planned behaviour. Decision support technologies aim at helping patients making informed treatment choices. Instruments assessing informed choices need to include risk knowledge, attitude… Read more »

Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation.

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

The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY.

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OBJECTIVES: Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis. METHODS: Transgenic NZM2328 mice were created by deletion of… Read more »

CD8-mediated inflammatory central nervous system disorders.

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PURPOSE OF REVIEW: In central nervous system (CNS) autoimmune disorders, CD8+ T cells have been reported to exert cytotoxic as well as regulatory functions. In virus-induced (meningo) encephalitis, they are essential for viral clearance, but can also cause severe immunopathology. This review aims to summarize the multifaceted roles CD8+ T cells can play in inflammatory… Read more »

MAPPIN’SDM–the multifocal approach to sharing in shared decision making.

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BACKGROUND: The wide scale permeation of health care by the shared decision making concept (SDM) reflects its relevance and advanced stage of development. An increasing number of studies evaluating the efficacy of SDM use instruments based on various sub-constructs administered from different viewpoints. However, as the concept has never been captured in operable core definition… Read more »

Elevated T2-values in MRI of stroke patients shortly after symptom onset do not predict irreversible tissue infarction.

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Distinct from signal alterations in diffusion-weighted images, T(2)-values are also dependent on tissue water content and known to increase with time from symptom onset in acute ischaemic stroke. The purpose of this study was to evaluate whether there is a detectable increase of T(2)-values in different regions in acute ischaemic stroke in the acute and… Read more »

Visual assessment of magnetic resonance imaging perfusion lesions in a large patient group.

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PURPOSE: Few magnetic resonance imaging (MRI) studies of stroke have evaluated the value of visual assessment of perfusion/diffusion mismatch, which is crucial for routine application. In this study an attempt was made to visually assess perfusion lesions resembling the acute clinical situation and identify parameters with the highest interobserver reliability when used to define a… Read more »

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression.

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both… Read more »

Sex-related factors in multiple sclerosis susceptibility and progression.

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

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

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

Quantitative T2′ imaging in patients with clinically isolated syndrome.

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OBJECTIVE: The T2′ imaging has been shown to be sensitive to oxygen saturation changes in normal appearing white and grey matter (NAWM, NAGM) in patients with relapsing-remitting multiple sclerosis (RRMS). We aimed to explore the presence and extent of T2′ changes in patients with a clinically isolated syndrome (CIS) and a possible association of T2′… Read more »

Cortical atrophy in experimental autoimmune encephalomyelitis: in vivo imaging.

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There are strong correlations between cortical atrophy observed by MRI and clinical disability and disease duration in multiple sclerosis (MS). The objective of this study was to evaluate the progression of cortical atrophy over time in vivo in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for MS. Volumetric changes in brains of… Read more »

Treatment of steroid-unresponsive optic neuritis with plasma exchange.

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OBJECTIVES: Until now, the significance of plasma exchange (PE) as a treatment for steroid-unresponsive optic neuritis (ON) is still unclear because placebo-controlled and larger studies are missing. We report our experience with 23 patients treated by PE due to steroid-unresponsive ON. MATERIALS AND METHODS: Patients were admitted to the University Medical Center Hamburg-Eppendorf between 2006… Read more »

Implementation of a patient education program on multiple sclerosis relapse management.

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OBJECTIVE: To study the implementation of a patient education program on relapses and relapse therapy into routine care. METHODS: 31 health care professionals took part in a one day train-the-trainer program (TTTP) and subsequently 261 persons with MS (pwMS) took part in the education program. Evaluation was carried out in trainers and pwMS. RESULTS: Participants… Read more »

Depressive syndromes in neurological disorders.

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Depressive syndromes represent a common and often characteristic feature in a number of neurological disorders. One prominent example is the development of post-stroke depression, which can be observed in more than one-third of stroke survivors in the aftermath of an ischemic stroke. Thus, post-stroke depression represents one of the most prevalent, disabling, and potentially devastating… Read more »

Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs.

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Multiple sclerosis is considered to be initiated by a deregulated, myelin-specific T cell response. However, the formation of inflammatory CNS lesions and the contribution of different leukocyte subsets in setting up these lesions are still incompletely understood. In this study, we show that, in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis, neutrophil granulocytes… Read more »

Plasma levels of neuron specific enolase quantify the extent of neuronal injury in murine models of ischemic stroke and multiple sclerosis.

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OBJECTIVE: We aimed at validating a plasma biomarker for neuronal damage that can be used in acute and chronic models of neurological diseases. METHODS: We investigated two different models, middle cerebral artery occlusion followed by reperfusion and MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). In stroke experiments we measured infarct sizes by magnetic resonance imaging and vital… Read more »

Role Preferences of People with Multiple Sclerosis: Image-Revised, Computerized Self-Administered Version of the Control Preference Scale.

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BACKGROUND: The Control Preference Scale (CPS) is the most frequently used measure of patients‘ preferred roles in treatment decisions. We revised the original CPS and developed a new computerized patient self-administered version (eCPS). We used the eCPS to assess role preferences, and their determinants, in Italian and German people with multiple sclerosis (MS). METHODS: New… Read more »

Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis.

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Multiple sclerosis (MS) is a devastating inflammatory disease of the brain and spinal cord that is thought to result from an autoimmune attack directed against antigens in the central nervous system. The aim of this first-in-man trial was to assess the feasibility, safety, and tolerability of a tolerization regimen in MS patients that uses a… Read more »

Patient autonomy in multiple sclerosis–possible goals and assessment strategies.

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Patient autonomy has been increasingly acknowledged as prerequisite for successful medical decision making in Western countries. In medical decisions with a need to involve a health professional, patient autonomy becomes apparent in the extent of patients‘ participation in the communication as described in the concept of shared decision making. Patient autonomy can be derived from… Read more »

Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.

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BACKGROUND: Prognostic counseling in multiple sclerosis (MS) is difficult because of the high variability of disease progression. Simultaneously, patients and physicians are increasingly confronted with making treatment decisions at an early stage, which requires taking individual prognoses into account to strike a good balance between benefits and harms of treatments. It is therefore important to… Read more »

Decision-making in multiple sclerosis consultations in Italy: third observer and patient assessments.

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OBJECTIVE: To assess decision-making in multiple sclerosis (MS) from third observer and patient perspectives. METHOD: Audio recordings of first-ever consultations with a participating physician (88 outpatients, 10 physicians) at four tertiary MS care clinics in Italy, were rated by a third observer using the Observing Patient Involvement in Shared Decision Making (OPTION) and by patients… Read more »

Comparison of 10 TTP and Tmax estimation techniques for MR perfusion-diffusion mismatch quantification in acute stroke.

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BACKGROUND AND PURPOSE: The mismatch between lesions identified in perfusion- and diffusion-weighted MR imaging is typically used to identify tissue at risk of infarction in acute stroke. The purpose of this study was to analyze the variability of mismatch volumes resulting from different time-to-peak or time-to-maximum estimation techniques used for hypoperfused tissue definition. MATERIALS AND… Read more »

The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

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The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing… Read more »

Association between cortisol awakening response and memory function in major depression.

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BACKGROUND: While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in… Read more »

Pregnancy and multiple sclerosis: feto-maternal immune cross talk and its implications for disease activity.

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system of presumed autoimmune origin. Intriguingly, pregnancy in female MS patients is associated with a substantial decrease in relapse rate. However, post-partum the relapse rate increases in a rebounding fashion above the rate seen before pregnancy. Wide gaps remain in our understanding of… Read more »

Comparison of patient-reported outcome measures in multiple sclerosis.

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BACKGROUND: Patient-reported outcome measurements (PROMS) have been proposed sensitive outcome parameters in multiple sclerosis (MS). In this study, we assessed a German version of the Multiple Sclerosis Impact Scale (MSIS-29) and a revised version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) in comparison with rater- and physician-based tools. METHODS: Consecutive MS… Read more »

A web-based tool for personalized prediction of long-term disease course in patients with multiple sclerosis.

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BACKGROUND AND PURPOSE: The Evidence-Based Decision Support Tool in Multiple Sclerosis (EBDiMS) is the first web-based prognostic calculator in multiple sclerosis (MS) capable of delivering individualized estimates of disease progression. It has recently been extended to provide long-term predictions based on the data from a large natural history cohort. METHODS: We compared the predictive accuracy… Read more »

Impaired social cognition in multiple sclerosis.

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BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the CNS that is frequently associated with neuropsychiatric symptoms and decreased quality of life. Social support, which has been found to buffer the psychosocial burden of MS, critically depends on intact social cognition. Here we assess social cognition in patients with MS using a… Read more »

A clinical and neurobiological case of IgM NMDA receptor antibody associated encephalitis mimicking bipolar disorder.

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Autoimmune encephalitis associated with IgG antibodies to the N-methyl-d-aspartic acid receptor subunit NR1 (NMDAR) presents with neurological symptoms, such as seizures, and especially psychiatric symptoms, such as hallucinations, psychosis, agitation and anxiety. To date, however, the pathological relevance of IgM NMDAR antibodies remains elusive. Here, we describe clinical, neuroradiological and neurobiological findings of a 28-year-old… Read more »

Critical role of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the development of inflammation-driven dermal fibrosis in a mouse model of systemic sclerosis.

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OBJECTIVE: To investigate the contribution of the adhesion receptor DNAX accessory molecule-1 (DNAM-1) in the development of dermal fibrosis on gene inactivation and targeted molecular strategies. METHODS: Human skin expression of DNAM-1 was determined by immunohistochemistry. Mice deficient for DNAM-1 (dnam1-/-) and wild-type controls (dnam1+/+) were injected with bleomycin or NaCl. Infiltrating leucocytes, T cells,… Read more »

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

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

Magnetic resonance imaging in multiple sclerosis–patients‘ experiences, information interests and responses to an education programme.

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BACKGROUND: Magnetic resonance imaging (MRI) is a key diagnostic and monitoring tool in multiple sclerosis (MS) management. However, many scientific uncertainties, especially concerning correlates to impairment and prognosis remain. Little is known about MS patients‘ experiences, knowledge, attitudes, and unmet information needs concerning MRI. METHODS: We performed qualitative interviews (n = 5) and a survey… 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 »

Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.

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BACKGROUND AND PURPOSE: Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in… Read more »

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

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

Aligning 3D time-of-flight MRA datasets for quantitative longitudinal studies: evaluation of rigid registration techniques.

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OBJECTIVE: 3D Time-of-flight (TOF) magnetic resonance angiography is commonly used for vascular analyses. A quantification of longitudinal morphological changes usually requires the registration of TOF image sequences acquired at different time points. The aim of this study was to evaluate the precision of different 3D rigid registration setups such that an optimal quantification of morphological… Read more »

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

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

A vaccine targeting mutant IDH1 induces antitumour immunity.

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Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour. They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG), genomic… Read more »

Influence of stroke infarct location on functional outcome measured by the modified rankin scale.

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BACKGROUND AND PURPOSE: In the early days after ischemic stroke, information on structural brain damage from MRI supports prognosis of functional outcome. It is rated widely by the modified Rankin Scale that correlates only moderately with lesion volume. We therefore aimed to elucidate the influence of lesion location from early MRI (days 2-3) on functional… Read more »

Adherence in multiple sclerosis (ADAMS): classification, relevance, and research needs. A meeting report.

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BACKGROUND: Adherence to medical interventions is a global problem. With an increasing amount of partially effective but expensive drug treatments adherence is increasingly relevant in multiple sclerosis (MS). Perceived lack of efficacy and side effects as well as neuropsychiatric factors such as forgetfulness, fatigue and depression are major determinants. However, research on adherence to behavioural… Read more »

Information provision for people with multiple sclerosis.

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

Acquired channelopathies as contributors to development and progression of multiple sclerosis.

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Multiple sclerosis (MS), the most frequent inflammatory disease of the central nervous system (CNS), affects about two and a half million individuals worldwide and causes major burdens to the patients, which develop the disease usually at the age of 20 to 40. MS is likely referable to a breakdown of immune cell tolerance to CNS… Read more »

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

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

Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis.

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

Visual and region of interest-based inter-rater agreement in the assessment of the diffusion-weighted imaging- fluid-attenuated inversion recovery mismatch.

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BACKGROUND AND PURPOSE: WAKE-UP is a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion’s visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) sequences as its main imaging inclusion criterion. Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement. We therefore sought… Read more »

Spatial distribution of perfusion abnormality in acute MCA occlusion is associated with likelihood of later recanalization.

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The aim of this study is to investigate whether different spatial perfusion-deficit patterns, which indicate differing compensatory mechanisms, can be recognized and used to predict recanalization success of intravenous fibrinolytic therapy in acute stroke patients. Twenty-seven acute stroke data sets acquired within 6 hours from symptom onset including diffusion- (DWI) and perfusion-weighted magnetic resonance (MR)… Read more »

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

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

Evidence-based patient information programme in early multiple sclerosis: a randomised controlled trial.

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OBJECTIVE: To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). BACKGROUND: Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice… Read more »

Reversible, irreversible and effective transverse relaxation rates in normal aging brain at 3T.

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Quantitative transverse relaxation rates in normal aging brain are essential to investigate pathologies associated with iron accumulation and tissue degeneration. Since absolute values depend on imaging methods and magnetic field strengths, continuous evaluation of specific reference values remains requisite. Multi-echo turbo spin echo and multi-echo gradient recalled echo imaging sequences were applied to 66 healthy… Read more »

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

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

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

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

Prediction of Infarction and Reperfusion in Stroke by Flow- and Volume-Weighted Collateral Signal in MR Angiography.

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BACKGROUND AND PURPOSE: In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive… Read more »

3T MRI Reveals Extra- and Intracranial Involvement in Giant Cell Arteritis.

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BACKGROUND AND PURPOSE: The frequency and amount of intracranial, intradural inflammatory vessel wall enhancement in giant cell arteritis remain unclear. The purpose of this work was to prospectively assess the intracranial extent of vasculitic changes in patients with giant cell arteritis using a dedicated MR imaging protocol optimized for assessment of mural changes of intracranial… Read more »