Duraisamy Kempuraj, Ramasamy Thangavel, Deepak D Kempuraj, Mohammad Ejaz Ahmed, Govindhasamy Pushpavathi Selvakumar, Sudhanshu P Raikwar, Smita A Zaheer, Shankar S Iyer, Raghav Govindarajan, Premkumar Nattanmai Chandrasekaran, Asgar Zaheer
Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases...
October 24, 2020: BioFactors
Alexandra Simbrich, Jasmine Thibaut, Laura Khil, Stanislav Maximov, Heinz Wiendl, Klaus Berger
The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS...
October 23, 2020: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Asli Koskderelioglu, Muhtesem Gedizlioglu, Neslihan Eskut, Pinar Tamer, Gizem Yalcin, Giray Bozkaya
INTRODUCTION: Plasma chemerin, which has chemotactic and adipogenic functions, is increased in several inflammatory diseases. However, its relationship with multiple sclerosis (MS) has not been explored yet. In this study, we aimed to determine chemerin levels and their possible role in MS. METHODS: Chemerin serum concentrations were evaluated by using ELISA kit in 91 clinically definite MS patients and 52 healthy controls. The mean serum chemerin, insulin, and cholesterol levels were compared...
October 24, 2020: Neurological Sciences
Juan Antonio García-León, Beatriz García-Díaz, Kristel Eggermont, Laura Cáceres-Palomo, Katrien Neyrinck, Rodrigo Madeiro da Costa, José Carlos Dávila, Anne Baron-Van Evercooren, Antonia Gutiérrez, Catherine M Verfaillie
Oligodendrocytes (OLs) are responsible for myelin production and metabolic support of neurons. Defects in OLs are crucial in several neurodegenerative diseases including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). This protocol describes a method to generate oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells (hPSCs) in only ~20 d, which can subsequently myelinate neurons, both in vitro and in vivo. To date, OPCs have been derived from eight different hPSC lines including those derived from patients with spontaneous and familial forms of MS and ALS, respectively...
October 23, 2020: Nature Protocols
Nellwyn Hagan, John L Kane, Deepak Grover, Lisa Woodworth, Charlotte Madore, Jacqueline Saleh, Jose Sancho, Jinyu Liu, Yi Li, Jonathan Proto, Matija Zelic, Amy Mahan, Michael Kothe, Andrew A Scholte, Maria Fitzgerald, Barbara Gisevius, Aiden Haghikia, Oleg Butovsky, Dimitry Ofengeim
Microglia serve as the innate immune cells of the central nervous system (CNS) by providing continuous surveillance of the CNS microenvironment and initiating defense mechanisms to protect CNS tissue. Upon injury, microglia transition into an activated state altering their transcriptional profile, transforming their morphology, and producing pro-inflammatory cytokines. These activated microglia initially serve a beneficial role, but their continued activation drives neuroinflammation and neurodegeneration. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, and activated microglia and macrophages play a significant role in mediating disease pathophysiology and progression...
October 23, 2020: Cell Death & Disease
Noelia Fernández Bargiela, Cristina Mondelo García, Víctor Giménez Arufe, José Ramón Vizoso Hermida, Isabel Martín Herranz
OBJECTIVES: Fingolimod is the first oral drug indicated in monotherapy as a modifier of the course of very active relapsing-remitting multiple sclerosis (RRMS). The safety profile of fingolimod is well established in clinical trials and post-marketing studies. Our objective was to study the profile of fingolimod use in our health area. METHODS: A retrospective, observational, descriptive study was performed on the use of fingolimod in adult patients diagnosed with RRMS between January 2015 and February 2017 or until suspension of treatment in a reference hospital in north-western Spain...
November 2020: European Journal of Hospital Pharmacy. Science and Practice
Diana Ferraro, Roberta Bedin, Patrizia Natali, Diego Franciotta, Krzysztof Smolik, Mario Santangelo, Paolo Immovilli, Valentina Camera, Francesca Vitetta, Matteo Gastaldi, Tommaso Trenti, Stefano Meletti, Patrizia Sola
BACKGROUND: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). METHODS: We enrolled patients who underwent a diagnostic spinal tap throughout two years...
October 21, 2020: Diagnostics
Liu Yang, Xinyan Han, Faping Xing, Hui Wu, Hailian Shi, Fei Huang, Qi Xu, Xiaojun Wu
BACKGROUND: Microglia-mediated neuroinflammation is one of the most prominent characteristics of multiple sclerosis (MS), a chronic demyelination disease. As one of the main active ingredients in Astragali radix, total flavonoids of Astragalus (TFA) has multiple pharmacological effects such as immunomodulation, anti-inflammation and and anti-tumor. However, little is known about whether TFA could inhibit microglia-mediated neuroinflammation in MS. PURPOSE: This study was aimed to elucidate whether TFA could inhibit microglia-mediated neuroinflammation in MS...
October 15, 2020: Phytomedicine
Antonio Barreiro-González, Maria T Sanz, Sara Carratalà-Boscà, Francisco Pérez-Miralles, Carmen Alcalá, Joan Carreres-Polo, Enrique España-Gregori, Bonaventura Casanova
OBJECTIVE: To investigate multiple sclerosis (MS) optical coherence tomography (OCT) cross-sectional correlations with central nervous system (CNS) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner (INL) and outer nuclear layer (ONL) of 54 relapsing remitting (RRMS) and 38 progressive (PMS, 9 primary and 29 secondary) patients were measured. With less than 3 months brain parenchymal fraction (BPF), spinal cord (SC), total gray matter (GM) and white matter volumes were calculated...
October 14, 2020: Journal of the Neurological Sciences
Roberto Bomprezzi, Andrew P Chen, Christopher C Hemond
OBJECTIVES: To answer the question whether cervical spondylosis would increase the incidence of cord lesions in MS patients, we investigated the statistical association between the two pathologies. METHODS: We extracted demographics, basic disease characteristics and MRI data of a cohort of 304 consecutive MS patients. For a subset of 176 patients, a detailed analysis independently assessed for each cervical level the co-existence of spinal canal narrowing from spondylosis and corresponding cord signal abnormalities...
October 15, 2020: Clinical Neurology and Neurosurgery
Cinzia Dello Russo, Kathryn Anne Scott, Munir Pirmohamed
Dimethyl fumarate (DMF) is a first line medication for multiple sclerosis. It has a favourable safety profile, however, there is concern regarding the occurrence of moderate-severe and sustained lymphopenia and the associated risk of progressive multifocal leukoencephalopathy. We carried out an extensive literature review to understand the molecular mechanisms underlying this adverse reaction. Dynamic changes in certain components of the immune system are likely to be important for the therapeutic effects of DMF, including depletion of memory T cells and decrease in activated T cells together with expansion of naïve T cells...
October 19, 2020: Pharmacology & Therapeutics
Jian Wang, Ivan Jelcic, Lena Mühlenbruch, Veronika Haunerdinger, Nora C Toussaint, Yingdong Zhao, Carolina Cruciani, Wolfgang Faigle, Reza Naghavian, Magdalena Foege, Thomas M C Binder, Thomas Eiermann, Lennart Opitz, Laura Fuentes-Font, Richard Reynolds, William W Kwok, Julie T Nguyen, Jar-How Lee, Andreas Lutterotti, Christian Münz, Hans-Georg Rammensee, Mathias Hauri-Hohl, Mireia Sospedra, Stefan Stevanovic, Roland Martin
The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells...
October 14, 2020: Cell
Martina Petruzzo, Antonio Reia, Giorgia Teresa Maniscalco, Fabrizio Luiso, Roberta Lanzillo, Cinzia Valeria Russo, Antonio Carotenuto, Lia Allegorico, Raffaele Palladino, Vincenzo Brescia Morra, Marcello Moccia
BACKGROUND: Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10-year risk of developing macrovascular disease. OBJECTIVE: To evaluate possible association between the Framingham risk score at baseline, and MS relapses, disability and disease-modifying therapy (DMT) choices over 5-year follow-up. METHODS: This is a retrospective cohort study including 251 MS subjects...
October 22, 2020: European Journal of Neurology
Giancarlo Comi, Amit Bar-Or, Hans Lassmann, Antonio Uccelli, Hans-Peter Hartung, Xavier Montalban, Per Solberg Sørensen, Reinhard Hohlfeld, Stephen L Hauser
The success of clinical trials of selective B-cell depletion in patients with relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) have led to a conceptual shift in the understanding of MS pathogenesis, away from the classical model in which T cells were the sole central actors, and towards a more complex paradigm with B cells having an essential role in both the inflammatory and neurodegenerative components of the disease process. The role of B cells in MS was selected as the topic of the 27th Annual meeting of the European Charcot Foundation...
October 9, 2020: Annals of Neurology
Hind Alnajashi, Razan Jabbad
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and Covid-19, a disease caused by SARS-CoV-2 became a pandemic in March 2020. As the pandemic still unfolds, uncertainty circles around the impact of SARS-CoV-2 infection on patients with chronic diseases, including autoimmune diseases such as multiple sclerosis (MS). To diminish the risk of SARS-CoV-2 infection and lessen the impact of the Covid-19 pandemic on the healthcare of MS patients, it is essential to understand knowledge, attitudes, and various behavioral practices related to Covid-19 among MS patients...
2020: PloS One
Ward Doelman, Mikkel H S Marqvorsen, Fabrizio Chiodo, Sven C M Bruijns, Gijsbert A van der Marel, Yvette van Kooyk, Sander Izaak van Kasteren, Can Araman
The protein myelin oligodendrocyte glycoprotein (MOG) is a key component of myelin and an autoantigen in the disease multiple sclerosis (MS). The posttranslational N-glycosylation of Asn31 of MOG seems to play a key role in modulating the immune response towards myelin. This is mediated by the interaction of Lewis type glycan structures on the N-glycan of MOG to the DC-SIGN receptor on dendritic cells (DCs). Here, we report the synthesis of an unnatural Lewis X (LeX) containing Fmoc-SPPS compatible asparagine building block, as well as asparagine building blocks containing two LeX derived oligosaccharides: LacNAc and Fucα1-3GlcNAc...
October 22, 2020: Chemistry: a European Journal
Cecilia Smith Simonsen, Heidi Øyen Flemmen, Line Broch, Cathrine Brunborg, Pål Berg-Hansen, Stine Marit Moen, Elisabeth Gulowsen Celius
OBJECTIVES: Over the past few decades, there has been an improvement in the rate of disability progression in multiple sclerosis (MS) patients, and most studies relate this evolvement to the introduction of disease-modifying therapies. However, several other factors have changed over this period, including access to MRI and newer diagnostic criteria. The aim of this study is to investigate changes in the natural course of MS over time in a near-complete and geographically well-defined population from the south-east of Norway...
October 22, 2020: Journal of Neurology
Theodore Peng, Nathaniel Gleason, Ralph Gonzales
Background/Introduction: Scheduled telephone follow-up visits (TFVs) are one strategy for improving access to specialty care practices, primarily because TFVs can be completed in less time with lower overhead costs than conventional office-based follow-up visits (OFVs). Beginning January 2015, scheduled TFVs were introduced in three specialty care practices at University of California San Francisco (UCSF) as a substitute for scheduled OFVs. As there is limited data on the relative advantage to patients from such a program, we conducted a survey to evaluate patient-reported outcomes associated with both TFVs and OFVs...
October 21, 2020: Telemedicine Journal and E-health
Nicolas J Guehl, Karla M Ramos-Torres, Clas Linnman, Sung-Hyun Moon, Maeva Dhaynaut, Moses Q Wilks, Paul K Han, Chao Ma, Ramesh Neelamegam, Yu-Peng Zhou, Brian Popko, John A Correia, Daniel S Reich, Georges El Fakhri, Peter Herscovitch, Marc D Normandin, Pedro Brugarolas
Demyelination causes slowed or failed neuronal conduction and is a driver of disability in multiple sclerosis and other neurological diseases. Currently, the gold standard for imaging demyelination is MRI, but despite its high spatial resolution and sensitivity to demyelinated lesions, it remains challenging to obtain specific and quantitative measures of molecular changes involved in demyelination. To understand the contribution of demyelination in different diseases and to assess the efficacy of myelin-repair therapies, it is critical to develop new in vivo imaging tools sensitive to changes induced by demyelination...
October 22, 2020: Journal of Cerebral Blood Flow and Metabolism
Imtiaz A Samjoo, Evelyn Worthington, Christopher Drudge, Melody Zhao, Chris Cameron, Dieter A Häring, Dee Stoneman, Luisa Klotz, Nicholas Adlard
Aim: To compare the efficacy of ofatumumab to other disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS). Materials & methods: A network meta-analysis was conducted to determine the relative effect of ofatumumab on annualized relapse rate and confirmed disability progression at 3 months and 6 months. Results: For each outcome, ofatumumab was as effective as other highly efficacious monoclonal antibody DMTs (i.e., alemtuzumab, natalizumab and ocrelizumab). Conclusion: Ofatumumab offers beneficial outcomes for RMS by reducing relapse and disability progression risk...
October 22, 2020: Journal of Comparative Effectiveness Research
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