Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis.

Background: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors.

Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course.

Cortical pathology in multiple sclerosis detected by the T1/T2-weighted ratio from routine magnetic resonance imaging.

Objective: In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown.

Methods: Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1- and T2-weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis.

A novel imaging technique for better detecting new lesions in multiple sclerosis.

We developed a tool that performs longitudinal subtraction of 3D double inversion recovery (DIR) images in follow-up magnetic resonance (MR) examinations of patients with multiple sclerosis. As DIR sequences show a high lesion-to-parenchyma contrast, we hypothesized that such a tool might lead to increased sensitivity for new lesions as well as to speeding up the routine clinical work-up of follow-up MR imaging in multiple sclerosis by directly visualizing new lesions. DIR subtraction images of serial MR examinations were calculated in 106 patients with multiple sclerosis.

Fatigue in multiple sclerosis: Associations with clinical, MRI and CSF parameters.

Background: Damage of different brain structures has been related to fatigue. Alternatively, functional alterations of central nervous system (CNS) cells by the inflammatory milieu within the CNS may be responsible for the development of fatigue.

Aim: To investigate the effect of structural brain damage and inflammatory cerebrospinal fluid (CSF) changes on fatigue in multiple sclerosis (MS).

Association of Retinal Architecture, Intrathecal Immunity, and Clinical Course in Multiple Sclerosis.

Importance: Biomarkers to estimate long-term outcomes in patients with multiple sclerosis (MS) and to assign patients to individual treatment regimens are urgently needed.

Objective: To assess whether retinal layer volumes are correlated with immune cell subsets and immunoglobulin indices in the cerebrospinal fluid and whether retinal layer volumes alone or in combination with intrathecal variables are associated with worsening of disease in patients with relapsing-remitting MS.

Design, Setting, And Participants: This observational cohort study included 312 patients with relapsing-remitting MS in 2 independent cohorts (72 patients with short disease duration [cohort 1] and 240 patients with longer disease duration [cohort 2]) treated at a single German university hospital from April 15, 2013, through November 11, 2015.

Intra- and interscanner variability of magnetic resonance imaging based volumetry in multiple sclerosis.

Brain volumetric measurements in multiple sclerosis (MS) reflect not only disease-specific processes but also other sources of variability. The latter has to be considered especially in multicenter and longitudinal studies. Here, we compare data generated by three different 3-Tesla magnetic resonance scanners (Philips Achieva; Siemens Verio; GE Signa MR750).

Prevalence of neuropathic pain in early multiple sclerosis.

Background: Pain is considered a frequent symptom in multiple sclerosis. Neuropathic pain is the type of pain most closely related to the pathology of multiple sclerosis and its prevalence estimates vary largely.

Objective: We prospectively assessed the prevalence of neuropathic pain in patients with early multiple sclerosis and investigated the association of neuropathic pain with other clinical parameters.

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients.

Spinal cord atrophy in early Huntington's disease.

Despite evidence for spinal cord involvement, it remains unclear whether spinal cord atrophy exists in early Huntington's disease. We studied magnetic resonance images, covering both brain and upper cervical cord, in two cohorts of Huntington's patients and in one cohort of Alzheimer's patients. All cohorts included healthy controls comparable with regard to age and gender.

Atrophy and structural variability of the upper cervical cord in early multiple sclerosis.

Background: Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) are conflicting.

Objective: To determine the onset of spinal cord atrophy in the disease course of MS.

Methods: Structural brain magnetic resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS (182) and 64 healthy controls (HCs).

Current and future therapies targeting the immune system in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The exact pathomechanism is unknown, but an aberrant immune response against CNS antigens, leading to inflammation in brain and spinal cord followed by demyelination, axonal damage and scar formation, seems to play a major role. Later in the disease course, inflammation decreases, while neurodegeneration proceeds.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls.

Brain size and white matter content of cerebrospinal tracts determine the upper cervical cord area: evidence from structural brain MRI.

Introduction: Measurement of the upper cervical cord area (UCCA) from brain MRI may be an effective way to quantify spinal cord involvement in neurological disorders such as multiple sclerosis. However, knowledge on the determinants of UCCA in healthy controls (HCs) is limited.

Methods: In two cohorts of 133 and 285 HCs, we studied the influence of different demographic, body-related, and brain-related parameters on UCCA by simple and partial correlation analyses as well as by voxel-based morphometry (VBM) across both cerebral gray matter (GM) and white matter (WM).

Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients.

Background: Treatment with natalizumab, a humanized monoclonal antibody against alpha4beta1 integrin, is associated with an increase in lymphoid progenitor cells and B cells in peripheral blood.

Objective: The objective of this study was to examine the impact of natalizumab therapy on serum levels of total IgG, IgA and IgM in patients with multiple sclerosis (MS).

Methods: In two independent cross-sectional patient cohorts, serum levels of IgG, IgA and IgM were compared between patients treated with natalizumab and those not receiving natalizumab.

The cytotoxicity of anti-CD22 immunotoxin is enhanced by bryostatin 1 in B-cell lymphomas through CD22 upregulation and PKC-βII depletion.

Background: In spite of potent first-line therapies for chronic lymphocytic leukemia, treatment remains palliative and all patients frequently relapse. Treatment options for these patients are more limited. BL22 is a recombinant protein composed of the variable region of a monoclonal antibody that binds to CD22 and of PE38, a truncated Pseudomonas exotoxin.