Safety, Patient-Reported Well-Being, and Physician-Reported Assessment of Walking Ability in Patients with Multiple Sclerosis for Prolonged-Release Fampridine Treatment in Routine Clinical Practice: Results of the LIBERATE Study.

Background: Prolonged-release fampridine (PR-FAM) 10-mg tablet twice daily is the only approved pharmacological treatment for improvement of walking ability in adults with multiple sclerosis (MS). LIBERATE assessed the safety/effectiveness of PR-FAM in the real-world.

Objectives: The aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged ≥ 65 years and those with pre-existing cardiovascular risk factors).

Vitamin D supplementation in multiple sclerosis: an expert opinion based on the review of current evidence.

Introduction: Vitamin D has long been known for its immune-modulating effects, next to its function in calcium metabolism. As a consequence, poor vitamin D status has been associated with many diseases including multiple sclerosis (MS). Epidemiological studies suggest an association between a poor vitamin D status and development of MS and a poor vitamin D status is associated with more relapses and faster progression after patients are diagnosed with MS.

Correlation of different cellular assays to analyze T cell-related cytokine profiles in vitamin D-supplemented patients with multiple sclerosis.

Different laboratory approaches have been exploited to analyze an effect of vitamin D supplements on T cell cytokine profiles in multiple sclerosis, with poorly reproducible results. We assessed the correlation between intra-cellular flowcytometry analysis of CD4 T cell-enriched CD3CD8 lymphocytes after PMA/ionomycin stimulation directly ex-vivo or after 72 h pre-stimulation with anti-CD3, and cytokine levels excreted in culture supernatants. Pre-stimulation with anti-CD3 resulted in higher proportions of cells positive for IFN-γ, IL-17 A, IL-4, IL-10 and GM-CSF (all P < 0.

Dimethyl fumarate treatment in multiple sclerosis: Recent advances in clinical and immunological studies.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which demyelination and neurodegeneration occurs. The immune system of MS patients is characterized by a dysregulation in the balance between pro- and anti-inflammatory immune cells, whereby both the innate and adaptive immune system are involved. Dimethyl fumarate (DMF) was licensed in 2013 as an oral first-line therapy for relapsing-remitting (RR)MS patients.

Dimethyl fumarate induces a persistent change in the composition of the innate and adaptive immune system in multiple sclerosis patients.

The effects of dimethyl fumarate (DMF) on the immune system in multiple sclerosis (MS) are not completely elucidated. In this study, an extensive immunophenotypic analysis of innate and adaptive immune cells of DMF-treated MS patients was performed. Peripheral blood immune cell phenotypes were determined using flow cytometry in a follow-up study of 12 MS patients before, after 3 and 12 months of DMF treatment and a cross-sectional study of 25 untreated and 64 DMF-treated MS patients.

Stress-Axis Regulation by Vitamin D in Multiple Sclerosis.

Introduction: Multiple sclerosis (MS) has been associated with both a poor vitamin D status and hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis. Since nuclear receptor ligands may regulate each other, we explored the association of vitamin D supplements with circadian cortisol levels in a double-blind and placebo-controlled supplementation study.

Methods: Female patients with relapsing-remitting MS received vitamin D supplements (4,000 IU/day;  = 22) or placebo ( = 19) during 16 weeks.

Vitamin D supplementation and the IL-2/IL-2R pathway in multiple sclerosis: Attenuation of progressive disturbances?

Vitamin D upregulates IL-2 receptor alpha (IL2RA, CD25)-expression on CD4 T cells in vitro. We investigated effects of 48-weeks vitamin D supplements on CD25-expression by CD4 T cells of patients with multiple sclerosis (MS). There was no significant difference between the vitamin D (n=30) and placebo group (n=23) in IL2RA mRNA-expression by PBMC.

Exploring the effect of vitamin D supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Background: Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS).

Objectives: To investigate the effect of high-dose vitamin D supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels.

Methods: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks.

Is the effect of coping styles disease specific? Relationships with emotional distress and quality of life in acquired brain injury and multiple sclerosis.

Objective: To investigate the use of coping styles and the relationships linking coping to emotional distress and quality of life in patients with acquired brain injury and multiple sclerosis.

Method: Cross-sectional cohort study of 143 patients with acquired brain injury and 310 patients with multiple sclerosis in the chronic stage. Quality of life was measured with the Life Satisfaction Questionnaire (LiSat-9), coping styles with the Coping Inventory for Stressful Situations (CISS-T, task-oriented; CISS-E, emotion-oriented; CISS-A, avoidance), emotional distress with the Hospital Anxiety and Depression Scale (HADS).

Vitamin D supplementation in multiple sclerosis: Symptoms and biomarkers of depression.

Depressive symptoms are common in multiple sclerosis (MS), and both depression and MS have been associated with a poor vitamin D status. As cytokine-mediated inflammatory processes play a role in the pathogenesis of both disorders, we hypothesized that vitamin D supplementation reduces depressive symptoms in MS via its immunomodulatory properties. In this randomized pilot study relapsing remitting (RR) MS patients received either vitamin D supplementation (n=20; 14.

Intake of tryptophan-enriched whey protein acutely enhances recall of positive loaded words in patients with multiple sclerosis.

Background & Aims: Multiple sclerosis (MS) has physiological and/or immunological characteristics that diminish serotonin metabolism, a neurotransmitter associated with affective and cognitive functions. The aim was examine the acute and dose-dependent effects of a dietary tryptophan (TRP) enrichment on affective and cognitive functions in MS patients. We hypothesized that increased dietary availability of the amino acid TRP enhances serotonin concentrations and improves neuropsychological functions.

Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients.

Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgDCD27 (double negative, DN) and CD21CD11c (CD21) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21 B cells in multiple sclerosis (MS) patients.

Immune regulatory effects of high dose vitamin D supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study.

Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D supplementation on clinical outcomes in a randomized controlled trial.

B cells of multiple sclerosis patients induce autoreactive proinflammatory T cell responses.

Antibody-independent B cell functions play an important role in multiple sclerosis (MS) pathogenesis. In this study, B cell antigen presentation and costimulation in MS were studied. Peripheral blood B cells of MS patients showed increased expression of costimulatory CD86 and CD80 molecules compared with healthy controls (HC).

Network of nuclear receptor ligands in multiple sclerosis: Common pathways and interactions of sex-steroids, corticosteroids and vitamin D3-derived molecules.

Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system.

Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up.

Background And Objective: The risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease.

Methods: This retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years.

Explaining fatigue in multiple sclerosis: cross-validation of a biopsychosocial model.

Fatigue is a common and disabling symptom in patients with multiple sclerosis (MS), but its pathogenesis is still poorly understood and consequently evidence-based treatment options are limited. Bol et al. (J Behav Med 33(5):355-363, 2010) suggested a new model, which explains fatigue in MS from a biopsychosocial perspective, including cognitive-behavioral factors.

B Cells Are Multifunctional Players in Multiple Sclerosis Pathogenesis: Insights from Therapeutic Interventions.

Multiple sclerosis (MS) is a severe disease of the central nervous system (CNS) characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production.

A low vitamin D status at diagnosis is associated with an early conversion to secondary progressive multiple sclerosis.

Low circulating 25-hydroxyvitamin D (25(OH)D) levels have been associated with an increased risk of relapses in relapsing remitting multiple sclerosis (RRMS), but an association with disability progression is uncertain. Lower 25(OH)D levels are found in secondary progressive MS (SPMS) when compared to RRMS. We hypothesized that a poor vitamin D status in RRMS is associated with an increased risk of conversion to SPMS.

GM-CSF production by CD4+ T cells in MS patients: regulation by regulatory T cells and vitamin D.

Background/objective: Data from animal models of MS suggest that GM-CSF(+)CD4(+)T cells are pathogenic cells. Therefore, GM-CSF production by CD4(+)T cells of MS patients and their susceptibility to regulatory mechanisms were investigated.

Methods: Intracellular flowcytometry was performed to determine the GM-CSF(+)CD4(+)T cell fraction in PBMC and CSF of MS patients and controls.

Vitamin D effects on B cell function in autoimmunity.

Vitamin D seems to be implicated in the pathophysiology of autoimmune disorders as a natural immune modulator. Beneficial effects of vitamin D have been associated with different cells of the immune system; however, thus far, B cells seem to be somewhat neglected. In this paper, we describe the possible direct effects of vitamin D on B cells, with a focus on antibody production and the more recently identified regulatory B (Breg ) cells.