Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of multiple sclerosis.

Molecular mechanisms that influence susceptibility to multiple sclerosis are poorly understood. We analyzed peripheral blood gene expression profiles in nine healthy subjects up to nine years before the onset of multiple sclerosis in comparison with 11 age-, gender-, and origin-matched healthy subjects who remained multiple sclerosis-free, and 31 subjects during the first clinical episode of multiple sclerosis. Within the 1051 highly variable genes that differentiated between multiple sclerosis-to-be and multiple sclerosis-free subjects, we identified activation of TCR signaling that triggered the Cbl and MAPK cascade in concert with downstream synergic over-expression of NFAT and MEF2B, but failed to augment the expression of the nuclear receptor gene family members NR4A1, NR2F1, VDR and MEF2B, that further resulted in impaired apoptotic machinery.

Molecular profiling of glatiramer acetate early treatment effects in multiple sclerosis.

Background: Glatiramer acetate (GA, Copaxone) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood.

Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC).

Clone clusters in autoreactive CD4 T-cell lines from probable multiple sclerosis patients form disease-characteristic signatures.

We developed a method for selectively propagating disease-related autoreactive T-cell lines (auTCLs) based on their increased resistance to apoptosis. The generated auTCLs homogeneously co-express CD45RO and CD49a, adhere strongly to extracellular matrix proteins and express high interleukin-17 (IL-17) messenger RNA levels, resembling a T-cell subset proposed to transmigrate into tissues and induce systemic and local inflammation in rheumatoid arthritis. The combinations of T-cell oligoclones that comprise probable multiple sclerosis (pMS) disease-related lines use a unique portfolio of T-cell receptor beta-chain variable allele (BV genes) combinations forming 'disease-specific cluster patterns'.

Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.

Background: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately.

Methods: In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS).

Gender effects in relapsing-remitting multiple sclerosis: correlation between clinical variables and gene expression molecular pathways.

Gene expression profiles were assessed in patients with relapsing-remitting multiple sclerosis (RRMS) to identify gender effects. Clear gender differences in time to second relapse and time to EDSS=6.0 progression in patients with late onset of the disease (>40years) were evident, and occurred more rapidly in female RRMS patients.

Happiness and neurological diseases.

Happiness is an emotional state reflecting positive feelings and satisfaction with life, which, as an outcome in disease states or as an end point in clinical trials, is a neglected concept in most therapeutic areas. In neurological disease, happiness is important as it can be diminished either as a direct result of damage to neuronal tissue or as a reaction to a poor prognosis. The monitoring and maintenance of happiness and wellbeing have historically been considered to be peripheral to medicine.

Effect of craniosacral therapy on lower urinary tract signs and symptoms in multiple sclerosis.

To examine whether craniosacral therapy improves lower urinary tract symptoms of multiple sclerosis (MS) patients. A prospective cohort study. Out-patient clinic of multiple sclerosis center in a referral medical center.

Lessons from randomised direct comparative trials.

For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-beta preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents.

Gait analysis in multiple sclerosis: characterization of temporal-spatial parameters using GAITRite functional ambulation system.

Background: Gait impairment is a significant problem in multiple sclerosis (MS), leading to decreased activity and limitations in function. However, specific characterization of abnormal gait in MS patients has only been described in small groups of patients, mainly using observational tools.

Objective: The aim of the current study was to characterize the spatio-temporal gait parameters in MS patients and ascribe them to clinical variables, in order to enable target-oriented management.

Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process.

Background And Purpose: Attention is one of the major cognitive domains adversely affected in multiple sclerosis (MS). The aim of the current study was to determine the effect of a single dose of methylphenidate on cognitive performance of MS patients with significant attention deficit.

Methods: In a double-blind placebo-controlled study design, 26 MS patients with impaired attention were randomly assigned to receive a single dose of 10 mg methylphenidate or placebo.

[Physical activity: positive impact on brain plasticity].

The central nervous system has a unique capability of plasticity that enables a single neuron or a group of neurons to undergo functional and constructional changes that are important to learning processes and for compensation of brain damage. The current review aims to summarize recent data related to the effects of physical activity on brain plasticity. In the last decade it was reported that physical activity can affect and manipulate neuronal connections, synaptic activity and adaptation to new neuronal environment following brain injury.

Breast cancer in women suffering from serious mental illness.

Background: Breast cancer is a major public health concern and the most common cause of cancer-related mortality among women. Compared with the general population, schizophrenia patients have been reported to have lower or similar rates of breast cancer despite several risk factors such as excess smoking, obesity and hyperprolactinemia. However, it has been argued that psychiatric morbidity itself may be the confounding factor that affects cancer incidence and not particularly schizophrenia.

Use of intravenous immunoglobulin in multiple sclerosis.

Intravenous immunoglobulin (IVIg) pooled from healthy human volunteers has a role in several immunomodulating mechanisms which may affect the pathogenesis of multiple sclerosis. Modulation of the disease course by IVIg is achieved both by limiting the inflammatory process and by enhancing remyelination. Clinical evidence of the effects of IVIg in multiple sclerosis is based on the results of several trials demonstrating the beneficial effects of IVIg on the relapse rate and on neurological disability.

Prolonged response times characterize cognitive performance in multiple sclerosis.

Cognitive impairment is amongst the main symptoms affecting multiple sclerosis (MS) and should be comprehensively and accurately assessed. To study the added value of a computerized neuropsychological battery enabling the measurement of response times in the cognitive domains, 58 randomly selected MS patients and 71 age-, gender- and education-matched healthy subjects were evaluated. Construct and discriminant validity were assessed for the standard Neuropsychological Screening Battery for Multiple Sclerosis (NSBMS) and the Mindstreams Computerized Cognitive Battery (MCCB).

Impaired expression of peripheral blood apoptotic-related gene transcripts in acute multiple sclerosis relapse.

Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with relapsing-remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic-related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro- and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission.

Zinc-ion binding and cytokine activity regulation pathways predicts outcome in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease characterized by an unpredictable clinical course with intermittent relapses that lead over time to significant neurological disability. Clinical and radiological variables are limited in the ability to predict disease course. Peripheral blood genome scale analyses were used to characterize MS patients with different disease types, but not for prediction of outcome.

Safety of intravenous immunoglobulin (IVIG) therapy.

Intravenous immunoglobulin (IVIg) is administered both for the treatment of immunodeficiencies and for an expanding list of autoimmune diseases. Most adverse effects are mild and transient including headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes and tachycardia. IgA deficiency-related anaphylactic reactions are largely preventable.

Dysregulation of affect in multiple sclerosis: new phenomenological approach.

Disorders involving regulation of affect commonly occur in multiple sclerosis (MS). These include various clinical presentations with inconsistent definitions that lead to many nomenclatures. In order to simplify the clinical approach to dysregulation of affect (DyA) a phenomenological definition was applied that unifies and combines the current classifications.

Long term safety of IVIg therapy in multiple sclerosis: 10 years experience.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. The majority of MS patients have a relapsing-remitting course with progressive neurological disability that accumulates over the years. Intravenous Immunoglobulin (IVIg) has demonstrated benefit in the treatment of some patients with relapsing-remitting MS.

Peripheral blood gene expression signature mirrors central nervous system disease: the model of multiple sclerosis.

Global gene expression analysis using cDNA microarrays has proven to be a sensitive method to gain insight into molecular pathways mediating multiple sclerosis (MS) activity and to develop and refine the molecular taxonomy of the disease. This method was applied as a tool to investigate molecular heterogeneity of MS related gene transcripts in the aim of distinguishing between transcripts that trigger disease activity and account for direct genotype-phenotype correlation, and those whose expression is altered as a downstream effect of other genes. This review summarizes the current state of gene expression microarray applications for the study of MS, and specifically emphasizes the results of gene expression studies using peripheral blood mononuclear cells (PBMC) that were shown to be useful for better understanding of disease related pathways, monitoring of therapeutic responses to various drugs and prediction of clinical outcome.

Perspectives in multiple sclerosis health care: special focus on the costs of multiple sclerosis.

Brain disorders are amongst the leading causes of disease and disability worldwide, accounting for 35% of the burden of all diseases in Europe. Despite their enormous personal and national impact the knowledge of the financial and economic impression of brain disorders has been relatively little researched. Recently it has been estimated that there are nearly 400,000 multiple sclerosis (MS) patients in Europe, which is 0.

Gene expression studies in systemic lupus erythematosus.

In a single assay, gene microarrays generate tens of thousands of measurements for the relative levels of messenger RNA expression, and thus hold promise to uncover the regulation of transcriptional responses behind clinical phenotypes of various diseases. Systemic lupus erythematosus (SLE) offers a unique opportunity to study gene expression both systemically and organ specific, as the tissues involved and specifically peripheral blood cells are readily accessible for molecular analysis. In the current review we highlight the current knowledge related to gene microarray in SLE.

Cognitive changes in early MS: a call for a common framework.

Cognitive dysfunction is among the main symptoms of multiple sclerosis (MS) and adversely affects patients' quality of life. The occurrence of cognitive impairment early in the disease process raises crucial issues related to definition of the impairment and its magnitude as well as to the tools applied to the assessment. To date there is little evidence concerning the reliability and validity of cognitive measures in early MS and their predictive long-term role.