Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in relapsing-remitting multiple sclerosis.

Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n = 116 and n = 26) and one dataset of treated patients with RRMS (n = 109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change.

Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis.

Background: Conventional brain MRI lesion measures have unreliable associations with clinical progression in multiple sclerosis (MS). Gray matter imaging may improve clinical-MRI correlations.

Methods: We tested if gray matter MRI measures and conventional measures of lesions/atrophy predicted clinical progression in a 4-year longitudinal study of 97 patients with MS.

Spinal cord lesions and clinical status in multiple sclerosis: A 1.5 T and 3 T MRI study.

Objective: Assess the relationship between spinal cord T2 hyperintense lesions and clinical status in multiple sclerosis (MS) with 1.5 and 3 T MRI.

Methods: Whole cord T2-weighted fast spin-echo MRI was performed in 32 MS patients [Expanded Disability Status Scale (EDSS) score (mean+/-SD: 2+/-1.

Daclizumab in treatment of multiple sclerosis patients.

Background: Daclizumab is a humanized monoclonal antibody (mAb) that blocks the interleukin-2 receptor alpha subunit (IL-2R-alpha chain; CD25) expressed on activated T cells leading to the inhibition of T-cell expansion, thus strongly reduces brain inflammation in patients with multiple sclerosis (MS). Another mechanism is significant expansion of CD56 (bright) natural killer (NK) cells that in turn inhibit T-cell survival.

Objective: At the Partners MS center, we have been using Daclizumab in an open-label fashion in patients who fail first line therapy or non-standard immunosuppressive treatment.

Unbiased treatment effect estimates by modeling the disease process of multiple sclerosis.

Gadolinium-enhancing lesions in the brain are commonly used as a primary outcome measure of disease activity in phase I/II clinical trials in multiple sclerosis (MS). The advent of effective therapy and the cost of clinical trials have led some researchers to adopt a one-arm study design with selection towards patients showing MRI activity. Regression to the mean is recognized as an important consideration in these trials, but the additional confounding effect of alternating active and inactive phases of disease has not been considered.

Role of iron in neurotoxicity: a cause for concern in the elderly?

Purpose Of Review: To explore the role of iron physiology in the brain of healthy adults and review how increased brain iron deposition has been associated with common neurodegenerative diseases that affect the elderly.

Recent Findings: Because iron plays a role in oxygen transportation, myelin synthesis, neurotransmitter production, and electron transfers, it serves as a crucial cofactor in normal central nervous metabolism. However, an increased level of brain iron may promote neurotoxicity due to free radical formation, lipid peroxidation, and ultimately, cellular death.

MRI in multiple sclerosis: what's inside the toolbox?

Magnetic resonance imaging (MRI) has played a central role in the diagnosis and management of multiple sclerosis (MS). In addition, MRI metrics have become key supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI measures have contributed to the understanding of MS pathophysiology at the macroscopic level yet have failed to provide a complete picture of underlying MS pathology.

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.

A magnetization transfer MRI study of deep gray matter involvement in multiple sclerosis.

Background/purpose: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS.

Design/methods: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs.

Cyclophosphamide therapy for MS.

Cyclophosphamide has been widely studied for the treatment of MS and the effective stabilization of selected patients on therapy has been suggested in several studies. This drug has selective effects on the immune response, such as suppression of helper Th1 activity and enhancement of helper Th2 responses; both of these processes are thought to be involved in the beneficial effect of cyclophosphamide in MS. Over the years, especially with the advent of magnetic resonance imaging (MRI), there has been an improved understanding of the profound anti-inflammatory effect of cyclophosphamide, evidenced by its effect on clinical relapses and contrast-enhancing lesions on MRI.

Imaging of multiple sclerosis: role in neurotherapeutics.

Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials.

Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis.

In recent years, it has become evident that the adult mammalian CNS contains a population of neural stem cells (NSCs) described as immature, undifferentiated, multipotent cells, that may be called upon for repair in neurodegenerative and demyelinating diseases. NSCs may give rise to oligodendrocyte progenitor cells (OPCs) and other myelinating cells. This article reviews recent progress in elucidating the genetic programs and dynamics of NSC and OPC proliferation, differentiation, and apoptosis, including the response to demyelination.