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Inflammatory Demyelinating Disease (inflammatory + demyelinating_disease)

Distribution by Scientific Domains

Medical Sciences	90%

Distribution within Medical Sciences

Neurology	55%
Pathology	33%

Selected Abstracts

Bilateral Internal Carotid Artery Dissection Mimicking Inflammatory Demyelinating Disease

JOURNAL OF NEUROIMAGING, Issue 4 2003
C. Lie MD
ABSTRACT Background and Purpose. Internal carotid artery (ICA) dissection (ICAD) may be extremely difficult to diagnose only on the basis of historical information and clinical signs, and even standard brain imaging (computed tomography [CT], T2-weighted magnetic resonance imaging [MRI]) may not be sufficient to delineate the underlying pathology clearly, as shown in this case. Methods. The clinical presentation and parenchymal lesion pattern on CT were suggestive of inflammatory demyelinating disease, and additional multiparametric MRI was per-formed. Results. Diffusion-weighted MRI, magnetic resonance angiography, and perfusion-weighted MRI revealed acute ischemic lesions, bilateral ICA obstruction, and bilateral hypoperfusion in the middle cerebral artery territories. Bilateral ICAD was confirmed by Doppler and duplex ultrasound, and anticoagulation therapy was initiated. A follow-up examination showed recanalization of the obstructed ICAs and the normalization of cerebral perfusion. Conclusion. This case illustrates the importance of demonstrating the pathology and the value of multiparametric MRI techniques for the diagnosis and monitoring of ICAD and its hemodynamic consequences. [source]

Simvastatin affects cell motility and actin cytoskeleton distribution of microglia

GLIA, Issue 2 2006
Hedwich F. Kuipers
Abstract Statin treatment is proposed to be a new potential therapy for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. The effects of statin treatment on brain cells, however, are hardly understood. We therefore evaluated the effects of simvastatin treatment on the migratory capacity of brain microglial cells, key elements in the pathogenesis of MS. It is shown that exposure of human and murine microglial cells to simvastatin reduced cell surface expression of the chemokine receptors CCR5 and CXCR3. In addition, simvastatin treatment specifically abolished chemokine-induced microglial cell motility, altered actin cytoskeleton distribution, and led to changes in intracellular vesicles. These data clearly show that simvastatin inhibits several immunological properties of microglia, which may provide a rationale for statin treatment in MS. © 2005 Wiley-Liss, Inc. [source]

Bilateral Internal Carotid Artery Dissection Mimicking Inflammatory Demyelinating Disease

Neuromyelitis optica/Devic's disease: Gene expression profiling of brain lesions

NEUROPATHOLOGY, Issue 6 2008
Jun-ichi Satoh
Neuromyelitis optica (NMO), also known as Devic's disease, is an inflammatory demyelinating disease that affects selectively the optic nerves and the spinal cord, possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Recent studies indicate that NMO also involves the brain. Here, we studied gene expression profile of brain lesions of a patient with NMO by using DNA microarray, along with gene expression profile of the brains of Parkinson disease and amyotrophic lateral sclerosis patients. We identified more than 200 genes up-regulated in NMO brain lesions. The top 20 genes were composed of the molecules closely associated with immune regulation, among which marked up-regulation of interferon gamma-inducible protein 30 (IFI30), CD163, and secreted phosphoprotein 1 (SPP1, osteopontin) was validated by real time RT-PCR, Northern blot and Western blot analysis. Pathologically, CD68+ macrophages and microglia expressed intense immunoreactivities for IFI30 and CD163 in NMO lesions, consisting of inflammatory demyelination, axonal loss, necrosis, cavity formation, and vascular fibrosis. KeyMolnet, a bioinformatics tool for analyzing molecular interaction on the curated knowledge database, suggested that the molecular network of up-regulated genes in NMO brain lesions involves transcriptional regulation by the nuclear factor-kappaB (NF-,B) and B-lymphocyte-induced maturation protein-1 (Blimp-1). These results suggest that profound activation of the macrophage-mediated proinflammatory immune mechanism plays a pivotal role in development of NMO brain lesions. [source]

Review: Mitochondria and disease progression in multiple sclerosis

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2008
D. Mahad
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Recent evidence suggests that dysfunction of surviving demyelinated axons and axonal degeneration contribute to the progression of MS. We review the evidence for and potential mechanisms of degeneration as well as dysfunction of chronically demyelinated axons in MS with particular reference to mitochondria, the main source of adenosine-5,-triphosphate in axons. Besides adenosine-5,-triphosphate production, mitochondria play an important role in calcium handling and produce reactive oxygen species. The mitochondrial changes in axons lacking healthy myelin sheaths as well as redistribution of sodium channels suggest that demyelinated axons would be more vulnerable to energy deficit than myelinated axons. A dysfunction of mitochondria in lesions as well as in the normal-appearing white and grey matter is increasingly recognized in MS and could be an important determinant of axonal dysfunction and degeneration. Mitochondria are a potential therapeutic target in MS. [source]

MHC Gene Related Effects on Microglia and Macrophages in Experimental Autoimmune Encephalomyelitis Determine the Extent of Axonal Injury

BRAIN PATHOLOGY, Issue 3 2002
Maria K. Storch
Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG-EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra-RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non-MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor-1 (AIF-1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u-haplotype in both the Class II and the telomeric non-classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a-haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC-region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE. [source]

Native and transformed ,2 -macroglobulin in plasma from patients with multiple sclerosis

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2003
M. Gunnarsson
Multiple sclerosis (MS) is an inflammatory demyelinating disease with unknown etiology. Various proteinases have been observed in increased levels in the central nervous system of patients with MS, which may contribute to the release of immunogenic myelin components. ,2 -Macroglobulin (,2M) inhibits a broad spectrum of proteinases sterically, undergoing major conformational changes induced by the proteinases themselves. Moreover, ,2M acts as a carrier of several cytokines in the systemic circulation. By use of radial immunodiffusion, we determined the total ,2M levels in plasma from 28 MS patients and 15 control subjects [14 patients with other neurologic diseases (OND) and one healthy individual]. No significant differences in total ,2M concentration were observed between the MS patients and the control subjects. A comparison of the degree of ,2M transformation in MS patients with different disease courses and controls was performed, using monoclonal antibodies (mAbs) specific for binding to native and transformed ,2M, respectively. The fractions of transformed ,2M were significantly increased in patients with secondary or primary progressive disease course compared with the controls. No significant differences were obtained using a native-specific mAb. At least a major proportion of ,2M from the MS patients was able to change conformation from its native to its transformed state, as demonstrated by a shift in mAb reactivity, following methylamine treatment of the plasma samples. In conclusion, the results indicate that plasma ,2M may be inactivated at a higher degree in patients with chronic progressive MS compared with patients with OND. This may influence the levels of proteinases and cytokines in the systemic circulation and may furthermore have diagnostic implications. [source]

Pathogenesis of Theiler's murine encephalomyelitis virus-induced disease

CLINICAL AND EXPERIMENTAL NEUROIMMUNOLOGY, Issue 2 2010
Raymond P. Roos
Abstract Theiler's murine encephalomyelitis virus (TMEV) is a member of the Cardiovirus genus of the Picornaviridae family. Interest in TMEV is at least partly related to the fact that the Daniels (DA) strain and other members of Theiler's original (TO) subgroup induce an inflammatory demyelinating disease in which the virus persists for the life of the mouse. This disease resembles multiple sclerosis because of the similar pathology and because the immune system seems to play an important role in both. The present review describes features of TMEV and the importance of both virus persistence as well as the immune system in the pathogenesis of DA virus-induced demyelinating disease. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759-1961.2010.00008.x, 2010) [source]

Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease,

ANNALS OF NEUROLOGY, Issue 6 2009
Fabienne Brilot PhD
Objective Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating diseases of the central nervous system (CNS). Although MOG is encephalitogenic in different animal models, the relevance of this antigen in human autoimmune diseases of the CNS is still controversial. Methods We investigated the occurrence and biological activity of antibodies to native MOG (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome [CIS], n = 28) by a cell-based bioassay. Results High serum immunoglobulin G (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the control children affected by other neurological diseases, healthy children, or adults with inflammatory demyelinating diseases, respectively. By contrast, IgM antibodies to nMOG occurred in only 3 children affected by ADEM. Children with high anti-nMOG IgG titer were significantly younger than those with low IgG titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and did not predict conversion from CIS to MS during a mean 2-year follow-up. However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS children. IgG antibodies to nMOG not only bound to the extracellular domain of nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing cells in vitro. Interpretation Overall, these findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS. Children may provide valuable insight into the earliest immune mechanisms of CNS demyelination. Ann Neurol 2009;66:833,842 [source]

Antibody-negative neuromyelitis optica with heavy B-cell infiltration

APMIS, Issue 10 2009
DANIEL BLACKBURN
There are several distinct clinical phenotypes of inflammatory demyelinating diseases of the central nervous system. In classical multiple sclerosis (MS) there are varied pathological patterns, possibly with differences in pathogenesis. Neuromyelitis optica (NMO) is often associated with a specific antibody, suggesting a distinct pathogenesis. We report a case of a young Caucasian male who presented with right hemiparesis secondary to a left fronto-parietal inflammatory brain lesion, which improved over years leaving minimal deficit. Seventeen years later he re-presented with a progressive tetraparesis secondary to cervical myelitis that did not respond to treatment. The NMO antibody was not detected and neuropathological examination was unusual with evidence of a persistent B-cell inflammatory response in the cord. Although having some of the clinical features of NMO, this case presented novel clinico-pathological features that do not easily fit into current MS subtypes. [source]