Simultaneous electroencephalographic and functional magnetic resonance imaging indicate impaired cortical top-down processing in association with anesthetic-induced unconsciousness.

Background: In imaging functional connectivity (FC) analyses of the resting brain, alterations of FC during unconsciousness have been reported. These results are in accordance with recent electroencephalographic studies observing impaired top-down processing during anesthesia. In this study, simultaneous records of functional magnetic resonance imaging (fMRI) and electroencephalogram were performed to investigate the causality of neural mechanisms during propofol-induced loss of consciousness by correlating FC in fMRI and directional connectivity (DC) in electroencephalogram.

Hunting for autoantibodies in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. Many findings support the assumption that the immune system plays a key role in the pathogenesis of MS, at least during the relapsing-remitting phase of disease.(1,2) Both arms of the adapted immune response seem to be crucial for the induction and maintenance of the autoimmune response as suggested by the success of therapies targeting T cells, B cells, or both.

MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.

Purpose: The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I-VIII). Within these lesion types, lesion types IV-V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones.

Exacerbation of experimental autoimmune encephalomyelitis by passive transfer of IgG antibodies from a multiple sclerosis patient responsive to immunoadsorption.

The pathogenic role of antibodies in multiple sclerosis (MS) is still controversial. We transferred to mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, IgG antibodies purified from a MS patient presenting a dramatic clinical improvement during relapse after selective IgG removal with immunoadsorption. Passive transfer of patient's IgG exacerbated motor paralysis and increased mouse central nervous system (CNS) inflammation and demyelination.

Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.

Background: Siponimod is an oral selective modulator of sphingosine 1-phosphate receptor types 1 and type 5, with an elimination half-life leading to washout in 7 days. We aimed to determine the dose-response relation of siponimod in terms of its effects on brain MRI lesion activity and characterise safety and tolerability in patients with relapsing-remitting multiple sclerosis.

Methods: In this double-blind, adaptive dose-ranging phase 2 study, we enrolled adults (aged 18-55 years) with relapsing-remitting multiple sclerosis at 73 medical centres in Europe and North America.

The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is thought to be a CD4+ T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential composition of immune cells within the CNS modulates age-associated susceptibility to CNS autoimmune disease.

Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis.

The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs).

Developmental maturation of innate immune cell function correlates with susceptibility to central nervous system autoimmunity.

MS is an inflammatory CNS disorder, which typically occurs in early adulthood and rarely in children. Here we tested whether functional maturation of innate immune cells may determine susceptibility to CNS autoimmune disease in EAE. Two-week-old mice were resistant to active EAE, which causes fulminant paralysis in adult mice; this resistance was associated with an impaired development of Th1 and Th17 cells.

Enriched CD161high CCR6+ γδ T cells in the cerebrospinal fluid of patients with multiple sclerosis.

Objective: To investigate the expression of CD161 (KLRB1) and CCR6 on human γδ T cells in blood and cerebrospinal fluid (CSF) of patients with a clinically isolated syndrome (CIS) and multiple sclerosis (MS) in relapse.

Design: Flow cytometry analysis of CD161 and CCR6 expression and intracellular cytokine staining for interleukin 17 and interferon-γ on human γδ T cells in blood and CSF samples.

Setting: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, a tertiary referral center.

White-matter lesions drive deep gray-matter atrophy in early multiple sclerosis: support from structural MRI.

Background: In MS, the relationship between lesions within cerebral white matter (WM) and atrophy within deep gray matter (GM) is unclear.

Objective: To investigate the spatial relationship between WM lesions and deep GM atrophy.

Methods: We performed a cross-sectional structural magnetic resonance imaging (MRI) study (3 Tesla) in 249 patients with clinically-isolated syndrome or relapsing-remitting MS (Expanded Disability Status Scale score: median, 1.

Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort.

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.

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.

Mitochondrial membrane protein associated neurodegenration: a novel variant of neurodegeneration with brain iron accumulation.

Background: Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN).

Methods/results: We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12.

Update on immunopathogenesis and immunotherapy in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Both genetic and environmental factors are believed to contribute to the pathogenesis of the disease. Histopathological findings suggest that multiple sclerosis is an immune-mediated disease, involving both the cellular and humoral immune systems.

Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis.

Objective: Intrathecal synthesis of immunoglobulin gamma (IgG) synthesis is frequently observed in patients with multiple sclerosis (MS). Whereas the extent of intrathecal IgG synthesis varies largely between patients, it remains rather constant in the individual patient over time. The aim of this study was to identify common genetic variants associated with the IgG index as a marker of intrathecal IgG synthesis in MS.

Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab "infusion group".

We observed two cases of progressive multifocal leukoencephalopathy (PML) that occurred in the same "infusion group". The group consisted of four patients with relapsing-remitting multiple sclerosis (RRMS) who had been treated with natalizumab (NAT) in the same medical practice for more than four years at the same times and in the same room, raising concerns about viral transmission between members of the infusion group. DNA amplification and sequence comparison of the non-coding control region (NCCR) of JC virus (JCV) present in cerebrospinal fluid (CSF) samples from PML patients #1 and #2 revealed that the amplified JCV sequences differed from the JCV archetype.

Spatiotemporal reconfiguration of large-scale brain functional networks during propofol-induced loss of consciousness.

Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging (fMRI), we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness (PI-LOC). After extraction of regional fMRI time series from 110 cortical and subcortical regions, we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain's intrinsic spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico-cortical and corticocortical connectivity.

Potassium channel KIR4.1 as an immune target in multiple sclerosis.

Background: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Many findings suggest that the disease has an autoimmune pathogenesis; the target of the immune response is not yet known.

Methods: We screened serum IgG from persons with multiple sclerosis to identify antibodies that are capable of binding to brain tissue and observed specific binding of IgG to glial cells in a subgroup of patients.

18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions.

Unlabelled: Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS.