Search results for "demyelinating"
showing 10 items of 60 documents
Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS.
2019
ObjectiveWe explored the incremental value of adding multiple disease activity biomarkers in CSF and serum for distinguishing MRI-based benign from aggressive MS in early disease course.MethodsNinety-three patients diagnosed with clinically isolated syndrome (CIS) or early MS were divided into 3 nonoverlapping severity groups defined by objective MRI criteria. Ninety-seven patients with noninflammatory neurologic disorders and 48 patients with other inflammatory neurologic diseases served as controls. Leukocyte subsets in the CSF were analyzed by flow cytometry. CSF neurofilament light chain (NfL) and chitinase-3-like protein 1 (CHI3L1) levels were measured by ELISA. Serum NfL levels were e…
Flow cytometric analysis of T cell/monocyte ratio in clinically isolated syndrome identifies patients at risk of rapid disease progression.
2015
Background: Multiple sclerosis is a chronic inflammatory central nervous system disease diagnosed by clinical presentation and characteristic magnetic resonance imaging findings. The role of cerebrospinal fluid (CSF) analysis has been emphasized in particular in the context of differential diagnosis in patients with a first episode suggestive of multiple sclerosis. Objective: We investigated here the potential additional value of analysis of CSF cellularity by fluorescence activated cell sorting (FACS) in the setting of a routine diagnostic work-up in our inpatient clinic. Methods: CSF cells from back-up samples from patients with suspected chronic inflammatory central nervous system disord…
Corrigendum: Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine mod…
2017
Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner…
DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning
2020
Genome-wide association studies (GWAS) identify genetic variants associated with traits or diseases. GWAS never directly link variants to regulatory mechanisms. Instead, the functional annotation of variants is typically inferred by post hoc analyses. A specific class of deep learning-based methods allows for the prediction of regulatory effects per variant on several cell type-specific chromatin features. We here describe “DeepWAS”, a new approach that integrates these regulatory effect predictions of single variants into a multivariate GWAS setting. Thereby, single variants associated with a trait or disease are directly coupled to their impact on a chromatin feature in a cell type. Up to…
PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders
2020
Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing–remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after …
The quality of cortical network function recovery depends on localization and degree of axonal demyelination
2016
AbstractMyelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies for ameliorating the course of such diseases usually focus on promoting remyelination, but the effectiveness of these approaches strongly depends on the timing in relation to the disease state. In this study, we sought to characterize the time course of sensory and behavioral alterations induced…
Inflammatory polyradiculoneuropathies: Clinical and immunological aspects, current therapies, and future perspectives
2020
Inflammatory polyradiculoneuropathies are heterogeneous disorders characterized by immune-mediated leukocyte infiltration of peripheral nerves and nerve roots leading to demyelination or axonal degeneration or both. Inflammatory polyradiculoneuropathies can be divided into acute and chronic: Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy and their variants. Despite major advances in immunology and molecular biology have been made in the last years, the pathogenesis of these disorders is not completely understood. This review summarizes the current literature of the clinical features and pathogenic mechanisms of inflammatory polyradiculoneuropathies and focuses…
Recovery from Toxic-Induced Demyelination Does Not Require the NG2 Proteoglycan
2016
NG2 cells are defined as CNS cells expressing chondroitin sulfate proteoglycan nerve/glia antigen. The vast majority of NG2-positive cells also express platelet-derived growth factor receptor alpha (PDGFRα) and are oligodendroglial progenitors (OPC). In addition a subpopulation of pericytes expresses NG2, but is positive for PDGF receptor beta (PDGFRβ) [1]. NG2-positive OPC comprise approximately 5% of the cells in the CNS where they are evenly distributed in grey and white matter [2, 3]. NG2-positive OPC form synapses with neurons [4–6] and react to brain injury with proliferation, as has been shown in several animal models as well as in human demyelinating and degenerative diseases [7–9].…
Time to activin on pathogenic T cells
2020
In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined. Here, using experimental autoimmune encephalomyelitis, an established mouse MS model, we report that therapeutic administration of activin-A ameliorates disease severity and alleviates CNS immunopathology and demyelination, associated with decreased activation of Th17 cells. In fact, activin-A signaling through activin-like kinase-4 receptor represses pathogenic t…
Sensitivity and specificity of a commercial ELISA test for anti-MAG antibodies in patients with neuropathy
2020
For the diagnosis of anti-MAG polyneuropathy the commercial ELISA manufacturer currently recommends a cut-off of 1000 Bühlmann Titer Units (BTU). We analyzed sera from 80 anti-MAG neuropathy patients and 383 controls (with other neuropathies or healthy controls) to assess the ELISA sensitivity and specificity at different thresholds. A better combination of sensitivity/specificity was found at a threshold >1500 BTU than at >1000 BTU. The best value of specificity was obtained at threshold >7000 BTU. There was a diagnostic grey area between 1500 and 7000 BTU in which the clinical phenotypes as well as electrophysiological studies need to be carefully assessed particularly to differe…