Thalamic atrophy and cognition in multiple sclerosis.

Objectives: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS.

The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL.

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab.

Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon beta-1a [INF beta]1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA.

Health-related quality of life in multiple sclerosis: effects of natalizumab.

Objective: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab.

Methods: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300 mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-beta-1a) plus natalizumab 300 mg (n = 589), or IFN-beta-1a plus placebo (n = 582).

Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.

Background: The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS.

Methods: 137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study.

Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor.

To investigate the association of the rs6265 (Val66Met) single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with brain morphometry and functional status as measured by quantitative magnetic resonance imaging (MRI) and neurocognitive testing in multiple sclerosis (MS) patients. BDNF is released by neurons and by immune cells in MS brain. The rs6265 SNP variation of BDNF causes substitution of valine (Val) for methionine (Met) and interferes with activity-dependent BDNF secretion.

Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis.

Following a previous study with diffusion tensor imaging, we investigated the correlation between diffusion-weighted imaging (DWI) and cognitive dysfunction in multiple sclerosis (MS). We studied 60 MS patients (mean age 45.8+/-9.

Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis.

Purpose: To investigate the relationship between immune cell secretion of brain-derived neurotrophic factor (BDNF) with clinical and MRI variables in multiple sclerosis (MS) patients.

Background: BDNF exerts beneficial effects on neuronal growth and repair and is secreted by both neurons and immune cells. Consequently, it may mediate the crosstalk between the immune system and CNS in autoimmune diseases such as MS.

Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis.

The primary goal of this study was to investigate associations between regional gray matter (GM) atrophy and neuropsychological function in multiple sclerosis (MS), while accounting for the influence of central brain atrophy (i.e. third ventricle enlargement).

Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients.

Background: Autoreactive antibodies (ARAB) occur more frequently in patients with multiple sclerosis (MS) than in general population and the presence of these antibodies often causes uncertainty regarding the disease course, response to therapy and the diagnosis of MS.

Methods: Retrospective analyses of the ARAB, clinical and MRI data of a consecutive patient cohort of MS and clinically isolated syndrome (CIS) patients were conducted. The patients were evaluated for an extensive panel that included various subtypes of antiphospholipid antibody (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti-SS-B antibodies.

Quantitative diffusion weighted imaging measures in patients with multiple sclerosis.

Diffusion-weighted imaging (DWI) has been proposed as a sensitive measure of disease severity capable of detecting subtle changes in gray matter and white matter brain compartments in patients with multiple sclerosis (MS). However, DWI has been applied to the study of MS clinical subtypes in only a few studies. The objective of this study was to demonstrate the validity of a novel, fully automated method for the calculation of quantitative DWI measures.

An association between autoreactive antibodies and anti-interferon-beta antibodies in multiple sclerosis.

Approximately 5-25% of interferon-beta (IFN-beta) treated multiple sclerosis (MS) patients develop anti-IFN-beta neutralizing antibodies (NAb) but the patient-specific variables associated with the risk of developing anti-IFN-beta antibodies are poorly understood. Anti-IFN-beta NAb are a subset of anti-IFN-beta binding antibodies (BAb) and all patients with NAb generally have high levels of associated BAb. The purpose of this research was to assess the association between autoreactive antibodies (ARAB) and the risk of developing anti-IFN-beta BAb in MS patients.

Treatment of pediatric multiple sclerosis and variants.

Studies in adult patients with multiple sclerosis (MS) suggest significant benefit of early treatment initiation. However, there are no approved therapies for children and adolescents with MS. For adult MS, tolerability and efficacy of several immunomodulatory and immunosuppressive drugs have been demonstrated.

MRI features of pediatric multiple sclerosis.

Background: MRI has revolutionized the diagnostic accuracy of multiple sclerosis (MS) in adults, and is now used extensively to evaluate efficacy of immunomodulatory therapies. Although MRI has also been used to aid in the diagnosis and care of children with MS, the MRI features of MS in children are less well understood.

Methods: The present review summarizes the available literature on MRI in pediatric MS, outlines the specific features of other disorders affecting the CNS white matter in children, compares the MRI appearance of MS in children to seminal neuroimaging studies in adult-onset MS, and discusses the potential role of advanced MRI technologies in delineating the underlying pathobiology of acquired demyelinating disease in children.

Clinical features of children and adolescents with multiple sclerosis.

There is increasing appreciation that multiple sclerosis (MS) can begin in childhood or adolescence, but pediatric MS continues to be a rare entity, with an estimated 2 to 5% of patients with MS experiencing their first clinical symptoms before age 16. A prompt diagnosis of pediatric MS is important to optimize overall management of both the physical and social impact of the disease. The widespread use of disease-modifying therapies (DMT) for MS in adults, as early as following an initial isolated episode, has led to the use of DMT in children and adolescents with MS.

Natalizumab reduces visual loss in patients with relapsing multiple sclerosis.

Objective: To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS).

Methods: AFFIRM and SENTINEL were randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy in AFFIRM and as add-on to interferon beta-1a in SENTINEL.

Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system that causes cognitive impairment with a frequency of roughly 50%. While processing speed and memory defects are most commonly observed, a substantial number of patients also have deficiency in higher executive ability. Two tests, the Wisconsin Card Sorting Test (WCST) and the Sorting Test from the Delis-Kaplan Executive Function System (DKEFS), have been recommended for evaluation of neuropsychological impairment in MS.

Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test.

Cognitive impairment is common in multiple sclerosis (MS), yet difficult to detect during routine neurologic examination. Therefore, brief screening tests that identify patients who may benefit from a more thorough assessment or treatment are needed. We investigated the utility of the Symbol Digit Modalities Test (SDMT) as a screen for cognitive dysfunction because it can be administered and scored in about 5 minutes.

Cyclophosphamide for multiple sclerosis.

Background: Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS.

Pharmacogenetics of MXA SNPs in interferon-beta treated multiple sclerosis patients.

The myxovirus resistance A (MXA) mRNA has been extensively investigated for assessing the biologic responses of multiple sclerosis (MS) patients to interferon-beta (IFN-beta) therapy. The objective of this study was to evaluate the associations between two MXA promoter region single nucleotide polymorphisms (rs2071430 and rs17000900) and the gene expression responses, clinical and MRI phenotypes in IFN-beta treated MS patients. The rs2071430 and rs17000900 SNPs, which are located in or near an interferon-stimulated response element (ISRE), were genotyped in 179 relapsing MS patients.

Interferon inhibitory activity in patients with multiple sclerosis.

Background: Interferon inhibitory activity (IIA) is a logical candidate for explaining neutralizing antibody-negative partial responsiveness to interferon beta in multiple sclerosis (MS), but its role has not been evaluated.

Objective: To investigate the role of IIA and soluble interferon-alpha/beta receptor (sIFNR) in determining response of patients with MS to interferon beta therapy.

Design: Parallel-group, open-label study.

Interferon-beta modulates bone-associated cytokines and osteoclast precursor activity in multiple sclerosis patients.

Purpose: Multiple sclerosis (MS) patients have a high risk of low bone density. The purpose of this study was to examine the molecular mechanisms potentially capable of modulating bone homeostasis in response to interferon-beta-1a (IFN-beta-1a) treatment and the focus was the bone-modulating system comprised of receptor activator of nuclear factor-kappaB (RANK), its ligand RANKL and its decoy receptor, osteoprotegerin (OPG).

Methods: In this open-label pharmacodynamic study, peripheral blood was obtained from relapsing-remitting MS patients just prior to and at multiple time points after intramuscular injection of 30 microg IFN-beta-1a.

Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).

Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis (MS). It is well known that processing speed and episodic memory deficits are the most common neuropsychological (NP) sequelae in this illness. Consensus has emerged about the specific tests that prove most helpful for routine monitoring of MS associated cognitive impairment.

Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis.

Background: Cognitive dysfunction is common in multiple sclerosis (MS). Correlations are reported between atrophy and neuropsychological test results.

Objective: To determine if neocortical volume would supplant or supplement third ventricular width and other magnetic resonance imaging measures when predicting neuropsychological impairment.

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls.