Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS.

Objective: To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS).

Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months.

When a pregnancy required a neurological consultation: a case report.

Posterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiological syndrome characterized by clinical signs and symptoms including hypertension, seizures, altered mental status, headache, and vision changes and characteristic features on head computed tomography (CT) or magnetic resonance imaging (MRI) scan. PRES is most commonly reported in the literature in association with obstetric patients suffering from pre-eclampsia or eclampsia. In the acute setting, it is important to recognize the characteristics of PRES and immediately treat patients' emerging conditions that are hypertension and seizures.

Epstein-Barr virus nuclear antigen-1 B-cell epitopes in multiple sclerosis twins.

Background: Compared with quantitative observations, the search for qualitative changes that may characterize the immune response to Epstein-Barr virus (EBV) in multiple sclerosis (MS) has been less intense.

Objective: To examine the B-cell epitopes of antibodies against the Epstein-Barr nuclear antigen-1 (EBNA-1) and their relevance for MS, through a study in disease-discordant identical twins.

Methods: We evaluated the antibodies to all unique, maximally overlapping octapeptides of EBNA-1 in 12 pairs of monozygotic (MZ) twins (9 MS-discordant, 3 healthy), 3 non-twin patients and 2 healthy subjects.

CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis.

To identify differentially expressed genes in multiple sclerosis, microarrays were used in a stringent experimental setting-leukapheresis from disease-discordant monozygotic twins and gene expression profiling in CD4(+) and CD8(+) T-cell subsets. Disease-related differences emerged only in the CD8(+) T-cell subset. The five differentially expressed genes identified included killer cell lectin-like receptor subfamily B, member 1, also known as natural killer receptor protein 1a/CD161, presented by the International Multiple Sclerosis Genetics Consortium as one of the non-MHC candidate loci.

Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial.

Background: The pleiotropic effects of riluzole may antagonize common mechanisms underlying chronic cerebellar ataxia, a debilitating and untreatable consequence of various diseases.

Methods: In a randomized, double-blind, placebo-controlled pilot trial, 40 patients presenting with cerebellar ataxias of different etiologies were randomly assigned to riluzole (100 mg/day) or placebo for 8 weeks. The following outcome measures were compared: proportion of patients with a decrease of at least 5 points in the International Cooperative Ataxia Rating Scale (ICARS) total score after 4 and 8 weeks compared with the baseline score; mean changes from the baseline to posttreatment ICARS (total score and subscores at 8 weeks); and occurrence of adverse events.

Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis.

Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance.

Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis.

Autoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS and T cell repertoire, peripheral blood CD4+ and CD8+ T lymphocytes and their CCR7+/CCR7- subsets from five pairs of identical twins (four discordant and one concordant for MS; none of which had taken disease-modifying therapy) were compared by TCR beta-chain (TCRB) complementary-determining region 3 (CDR3) spectratyping.

Multiple sclerosis: pharmacogenomics and personalised drug treatment.

Multiple sclerosis (MS) is a disorder of the central nervous system with an inflammatory and a neurodegenerative component. We do not yet have a definitive therapy for MS. Attempts to develop new treatments are long and costly and should be paralleled by studies aimed at increasing the therapeutic index of the existing treatments, interferon beta and glatiramer acetate.

Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: a six-month longitudinal follow-up study.

Twenty-six chemical elements and oxidative status were determined in serum of 12 patients with first demyelinating episode and brain magnetic resonance imaging compatible with the disease at different time points. Quantifications of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, V, Tl, W, Zn and Zr, as well as of serum oxidative status and antioxidant capacity were carried out. The results were compared with values obtained from healthy subjects living in the same geographic area.

Quantification of chemical elements in blood of patients affected by multiple sclerosis.

Although some studies suggested a link between exposure to trace elements and development of multiple sclerosis (MS), clear information on their role in the aetiology of MS is still lacking. In this study the concentrations of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, Tl, V, W, Zn and Zr were determined in the blood of 60 patients with MS and 60 controls. Quantifications were performed by inductively coupled plasma (ICP) atomic emission spectrometry and sector field ICP mass spectrometry.

Multiple sclerosis in twins from continental Italy and Sardinia: a nationwide study.

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.

Cerebrospinal fluid isoprostanes are not related to inflammatory activity in relapsing-remitting multiple sclerosis.

Oxidative stress leads to lipid peroxidation and may contribute to the pathogenesis of lesions in multiple sclerosis (MS), an autoimmune disease characterised by inflammatory as well as degenerative phenomena. We previously found that cerebrospinal fluid (CSF) levels of isoprostane 8-epi-PGF2alpha, a marker of free radical damage and lipid peroxidation in vivo, were elevated in MS patients. Such levels were correlated with the degree of disability and reduced in subjects under steroid therapy.

[Twins in biomedical research and the creation of the "National Twin Registry"].

Twins are a valuable resource for the study of complex traits. The twin method is substantially based on the comparison between correlations and concordance in monozygotic (MZ) and dizygotic (DZ) twins and allows several applications in biomedical and molecular genetic research. It allows either the qualitative and quantitative evaluation of the influences that genetic and environmental factors exert on phenotypes or the estimation of trait variability.

Physiopathology of multiple sclerosis.

Pleiotropy and redundancy are distinctive elements of the immune response. Recent research into the inflammatory component of multiple sclerosis (MS) indicates that, as expected, pleiotropy and redundancy characterize various physiopathological mechanisms of the disease. A certain degree of redundancy is becoming apparent also as far as the degenerative component is concerned.

A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population.

We have systematically screened the genome for evidence of linkage disequilibrium (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case-control and family based (AFBAC) cohorts from the Italian population. DNA pooling was used to reduce the genotyping effort involved. Four DNA pools were considered: cases (224 Italian MS patients), controls (231 healthy Italians), index (185 index cases from trio families) and parents (the 370 parents of the patient included in the Index pool), respectively.

T cell response to amyloid-beta and to mitochondrial antigens in Alzheimer's disease.

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer's disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1-42 of amyloid-beta (Abeta) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled.

Prolactin and prolactin receptor gene polymorphisms in multiple sclerosis and systemic lupus erythematosus.

Genes encoding for prolactin (PRL) and its receptor (PRLR) are possible candidates for multiple sclerosis (MS) and systemic lupus erythematosus (SLE) susceptibility. In fact: (1) a prolactin secretion dysfunction has been described in several autoimmune diseases including SLE and MS and their animal models; (2) both PRL and PRLR are structurally related to members of the cytokine/hematopoietin family and have a role in the regulation of the immune response; and (3) both PRL and PRLR genes map in genomic regions that showed linkage with autoimmunity. Prolactin maps on chromosome 6p, about 11-kb telomeric to HLA-DRB1 and PRLR in 5p12-13, which revealed evidence of linkage with MS in different populations.

The Italian Twin Project: from the personal identification number to a national twin registry.

The unique opportunity given by the "fiscal code", an alphanumeric identification with demographic information on any single person residing in Italy, introduced in 1976 by the Ministry of Finance, allowed a database of all potential Italian twins to be created. This database contains up to now name, surname, date and place of birth and home address of about 1,300,000 "possible twins". Even though we estimated an excess of 40% of pseudo-twins, this still is the world's largest twin population ever collected.

Protein tyrosine phosphatase receptor-type C exon 4 gene mutation distribution in an Italian multiple sclerosis population.

In this study, we investigate the role of the C-->G mutation in position 77 of exon 4 of the protein tyrosine phosphatase receptor-type C (PTPRC) gene, coding for the CD45 molecule, for the development of multiple sclerosis (MS) in an Italian continental population. The PTPRC mutated genotype has been recently described as associated with MS in three different case-control studies carried out in German MS patients, whereas similar studies performed in the US and Swedish populations failed to demonstrate such an association. The C-->G transition in position 77 was found in a small number of Italian MS patients and in none of the matched group of healthy controls (Fisher exact test, P value=0.

Epidemiology and current treatment of multiple sclerosis in Europe today.

Multiple sclerosis (MS) is a chronic disease affecting the central nervous system, usually leading to early disablement in young adults. At least 350,000 persons in Europe have the disease. Wide variations exist both between and within European countries in the incidence and prevalence of the disease as well as in the general standard of care for MS patients.

Identification of single nucleotide variations in the coding and regulatory regions of the myelin-associated glycoprotein gene and study of their association with multiple sclerosis.

The myelin-associated glycoprotein (MAG) gene is an appealing candidate in the 19q13 Multiple Sclerosis (MS) candidate region. Using denaturing high performance liquid chromatography (DHPLC), we identified 14 single nucleotide polymorphisms (SNPs) in MAG coding and regulatory regions, and we tested their possible association with MS in Italian patient and control DNA pools. Eight variations had a frequency <0.

T cell response to N-formylated peptides in humans.

We present the first evidence of a T lymphocyte response to N-formylated peptides in humans. N-formylated peptide sequences from self (mitochondrial) and foreign (microbial) antigens were used to isolate antigen-specific T cell clones from healthy individuals, including a set of monozygotic twins. The observed response differed from that previously described in mouse (CD4(+) phenotype and MHC class II restriction in humans vs.

Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis.