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Demyelinating disease

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https://www.readbyqxmd.com/read/29457657/semaphorin4a-and-h-ferritin-utilize-tim-1-on-human-oligodendrocytes-a-novel-neuro-immune-axis
#1
Brian Chiou, Elisabeth Lucassen, Michael Sather, Asha Kallianpur, James Connor
Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect...
February 19, 2018: Glia
https://www.readbyqxmd.com/read/29456537/understanding-progressive-multifocal-leukoencephalopathy-risk-in-multiple-sclerosis-patients-treated-with-immunomodulatory-therapies-a-bird-s-eye-view
#2
REVIEW
Elizabeth A Mills, Yang Mao-Draayer
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29455558/investigational-immunosuppressants-in-early-stage-clinical-trials-for-the-treatment-of-multiple-sclerosis
#3
Alberto Gajofatto, Marco Turatti
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS...
February 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29455184/csf-free-light-chain-identification-of-demyelinating-disease-comparison-with-oligoclonal-banding-and-other-csf-indexes
#4
Kari M Gurtner, Eslam Shosha, Sandra C Bryant, Bruna D Andreguetto, David L Murray, Sean J Pittock, Maria Alice V Willrich
BACKGROUND: Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. METHODS: A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured...
February 19, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29454521/hepatitis-b-vaccination-and-the-putative-risk-of-central-demyelinating-diseases-a-systematic-review-and-meta-analysis
#5
Julie Mouchet, Francesco Salvo, Emanuel Raschi, Elisabetta Poluzzi, Ippazio Cosimo Antonazzo, Fabrizio De Ponti, Bernard Bégaud
BACKGROUND: The anti-hepatitis B immunization campaigns launched in the early 1990s were a major public health breakthrough and targeted various populations (at-risk adults, newborns, adolescents). However, debate is still active about a possible link between this vaccine and central demyelination. This study provides a pooled estimate of this risk based on a comprehensive review and meta-analysis of all available epidemiologic studies. METHODS: A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from database inception to 10 May 2017...
February 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29454471/severe-course-of-neuromyelitis-optica-in-a-female-patient-with-chronic-c-hepatitis
#6
Krystian Obara, Marta Waliszewska-Prosół, Sławomir Budrewicz, Paweł Szewczyk, Maria Ejma
Neuromyelitis optica (NMO) is a rare, disabling, recurring inflammatory demyelinating disease affecting the spinal cord and optic nerves with predominance in women. We present the case of a female patient with chronic C hepatitis, who, despite treatment, developed severe symptoms of NMO during pregnancy and postpartum.
February 6, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29453889/mitochondrial-dysfunction-and-axon-degeneration-in-progressive-multiple-sclerosis
#7
REVIEW
Graham Campbell, Don Mahad
The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons...
February 17, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29449193/phase-i-trial-of-intrathecal-mesenchymal-stem-cell-derived-neural-progenitors-in-progressive-multiple-sclerosis
#8
Violaine K Harris, James Stark, Tamara Vyshkina, Leslie Blackshear, Gloria Joo, Valentina Stefanova, Gabriel Sara, Saud A Sadiq
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS. METHODS: We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS...
February 3, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29448957/brain-region-specific-enhancement-of-remyelination-and-prevention-of-demyelination-by-the-csf1r-kinase-inhibitor-blz945
#9
Nicolau Beckmann, Elisa Giorgetti, Anna Neuhaus, Stefan Zurbruegg, Nathalie Accart, Paul Smith, Julien Perdoux, Ludovic Perrot, Mark Nash, Sandrine Desrayaud, Peter Wipfli, Wilfried Frieauff, Derya R Shimshek
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29445325/biomarkers-of-amyotrophic-lateral-sclerosis-current-status-and-interest-of-oxysterols-and-phytosterols
#10
REVIEW
Anne Vejux, Amira Namsi, Thomas Nury, Thibault Moreau, Gérard Lizard
Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29445144/lenalidomide-regulates-cns-autoimmunity-by-promoting-m2-macrophages-polarization
#11
Qinjie Weng, Jiaying Wang, Jiajia Wang, Jing Wang, Fahmida Sattar, Zhikang Zhang, Jiahuan Zheng, Zijie Xu, Mengting Zhao, Xuan Liu, Lijun Yang, Guifeng Hao, Liang Fang, Q Richard Lu, Bo Yang, Qiaojun He
Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444796/biopsy-proven-multiple-sclerosis-in-an-adult-patient-with-atypical-craniometaphyseal-dysplasia
#12
Jacopo C DiFrancesco, Giuseppe Isimbaldi, Maria Francesca Bedeschi, Barbara Castellotti
Craniometaphyseal dysplasia (CMD) is a rare condition characterised by progressive, diffuse hyperostosis of cranial and long bones, with compression of cranial nerves, linked to mutations in ANKH or GJA1 genes. Here we describe an adult case with clinical features of CMD, who developed cerebral expansive lesion of undetermined nature. Brain biopsy revealed active demyelinating lesions, consistent with multiple sclerosis. The genetic screening of target genes for CMD ( ANKH and GJA1 ) resulted negative in this patient...
February 14, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29444299/early-nodal-and-paranodal-disruption-in-autoimmune-optic-neuritis
#13
Aleksandar Stojic, Jovana Bojcevski, Sarah K Williams, Ricarda Diem, Richard Fairless
Disturbances in the nodes of Ranvier are an early phenomenon in many CNS disorders, including the autoimmune demyelinating disease multiple sclerosis (MS). Using an animal model of optic neuritis, a common early symptom of MS, we have investigated nodal and paranodal compartments in the optic nerve during disease progression. Both nodes and paranodes, as identified by immunohistochemistry against sodium channels (Nav) and Caspr, respectively, were observed to increase in length during the late induction phase of the disease, prior to onset of the demyelination and immune cell infiltration characteristic of optic neuritis...
February 10, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29443442/paediatric-adem-followed-by-optic-neuritis-disease-course-treatment-response-and-outcome
#14
Y Y M Wong, Y Hacohen, T Armangue, E Wassmer, H Verhelst, C Hemingway, E D van Pelt, C E Catsman-Berrevoets, R Q Hintzen, K Deiva, M J Lim, K Rostásy, R F Neuteboom
BACKGROUND: Acute disseminated encephalomyelitis, followed by optic neuritis (ADEM-ON) is a rare demyelinating syndrome different than MS and neuromyelitis optica spectrum disorder. We aim to describe the disease course, treatment response and outcome of these children. METHODS: children <18 years were identified from 6 countries of the EU Paediatric Demyelinating Disease Consortium. Patients fulfilled the diagnostic criteria for ADEM, followed by at least one ON...
February 14, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29441412/progressive-multiple-sclerosis-patients-show-substantial-lesion-activity-that-correlates-with-clinical-disease-severity-and-sex-a-retrospective-autopsy-cohort-analysis
#15
Sabina Luchetti, Nina L Fransen, Corbert G van Eden, Valeria Ramaglia, Matthew Mason, Inge Huitinga
Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected...
February 13, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29440322/neurodegeneration-in-progressive-multiple-sclerosis
#16
Graham Campbell, Don Mahad
The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating molecular changes within neuronal cell bodies. All of these molecular changes to intrinsic neurons converge on mitochondria, and the most reproduced change relates to mitochondrial respiratory chain complex deficiency. This compromise in the capacity to generate ATP in the neuronal cell body is coupled with an increased demand for energy by the demyelinated axon, which is particularly relevant to the long tracts such as corticospinal tracts with long projection axons...
February 12, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29439122/iron-insensitive-quantitative-assessment-of-subcortical-gray-matter-demyelination-in-multiple-sclerosis-using-the-macromolecular-proton-fraction
#17
V L Yarnykh, E P Krutenkova, G Aitmagambetova, P Repovic, A Mayadev, P Qian, L K Jung Henson, B Gangadharan, J D Bowen
BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping. MATERIALS AND METHODS: Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging...
February 8, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29438836/mog-antibody-demyelinating-diseases-a-case-of-post-partum-severe-rhombencephalitis-and-transverse-myelitis
#18
D Vecchio, E Virgilio, P Naldi, C Comi, R Cantello
INTRODUCTION: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) associated disorders present with a spectrum of clinical pictures including brainstem involvement. CASE REPORT: A patient with the sudden onset of a post-partum severe rhombencephalitis causing respiratory failure (12 years after a mild transverse myelitis). Despite the aggressive clinical course, she had an impressive recovery after plasmapheresis, and no further relapses on immunosuppression...
February 8, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29438266/new-ways-of-seeing-the-mechanistic-heterogeneity-of-multiple-sclerosis-plaque-pathogenesis
#19
Ethan I Meltzer, Fiona E Costello, Elliot M Frohman, Teresa C Frohman
BACKGROUND: Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments...
March 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29438265/keep-your-eyes-wide-open-on-visual-and-vision-related-measurements-to-better-understand-multiple-sclerosis-pathophysiology
#20
Yael Backner, Netta Levin
BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is multifaceted. It manifests as acute episodes as well as an accumulative chronic disability; myelin involvement as well as axonal damage; local as well as global effects; and disease load elements as well as compensatory mechanisms. The visual system, with its clear structural organization and relatively direct reflection of damage, may serve as an appropriate model to study MS. METHODS: In recent years, we have witnessed a blossoming in the field of visual measures in MS...
March 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
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