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'Multiple Sclerosis'

Laura Dumitrescu, Cris S Constantinescu, Radu Tanasescu
Multiple sclerosis (MS) is a chronic central nervous system immune-mediated disease with an important inflammatory component associated with focal demyelination and widespread neurodegeneration. In most cases, the clinical presentation is relapsing-remitting, followed by a secondary progressive phase, characterized by disability accrual unrelated to relapses. In a minority, the phenotype is progressive from the beginning. Major therapeutic achievements have been made concerning the relapsing phase but modifying the evolution of progressive MS remains an unmet need...
December 5, 2018: Expert Opinion on Pharmacotherapy
Frank Konietschke, Tim Friede, Markus Pauly
Count data are common endpoints in clinical trials, for example magnetic resonance imaging lesion counts in multiple sclerosis. They often exhibit high levels of overdispersion, that is variances are larger than the means. Inference is regularly based on negative binomial regression along with maximum-likelihood estimators. Although this approach can account for heterogeneity it postulates a common overdispersion parameter across groups. Such parametric assumptions are usually difficult to verify, especially in small trials...
December 5, 2018: Biometrical Journal. Biometrische Zeitschrift
Andreas Johnen, Paul-Christian Bürkner, Nils C Landmeyer, Björn Ambrosius, Pasquale Calabrese, Jeremias Motte, Nicole Hessler, Gisela Antony, Inke R König, Luisa Klotz, Muna-Miriam Hoshi, Lilian Aly, Sergiu Groppa, Felix Luessi, Friedemann Paul, Björn Tackenberg, Florian Then Bergh, Tania Kümpfel, Hayrettin Tumani, Martin Stangel, Frank Weber, Antonios Bayas, Brigitte Wildemann, Christoph Heesen, Uwe K Zettl, Frauke Zipp, Bernhard Hemmer, Sven G Meuth, Ralf Gold, Heinz Wiendl, Anke Salmen
BACKGROUND: Cognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis. METHODS: Neuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes...
December 4, 2018: Journal of Neurology
E D'Amico, A Zanghì, M Sciandra, G Borriello, G Callari, A Gallo, G Salemi, S Cottone, M Buccafusca, P Valentino, R B Bossio, L M E Grimaldi, C Pozzilli, G Tedeschi, M Zappia, F Patti
BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome...
December 4, 2018: Journal of Neurology
Thor Ameri Chalmer, Tomas Kalincik, Bjarne Laursen, Per Soelberg Sorensen, Melinda Magyari
BACKGROUND: Patients with multiple sclerosis who experience disease breakthrough often switch disease-modifying therapy (DMT). OBJECTIVE: To compare treatment effectiveness of switch to highly effective DMT (heDMT) with switch to moderately effective DMT (meDMT) for patients who switch due to disease breakthrough defined as at least one relapse within 12 months of their treatment switch. METHODS: We retrieved data from The Danish Multiple Sclerosis Registry on all relapsing-remitting MS patients with expanded disability status scale (EDSS) less than 6 who experienced disease breakthrough...
December 4, 2018: Journal of Neurology
I C Hasselbalch, H B Søndergaard, N Koch-Henriksen, A Olsson, H Ullum, F Sellebjerg, A B Oturai
Background: Subtypes of white blood cell counts are known biomarkers of systemic inflammation and a high neutrophil-to-lymphocyte ratio (NLR) has been associated with several autoimmune diseases. Few studies have investigated the NLR in multiple sclerosis (MS). Objective: To examine the association between NLR, MS and disability measured by the MS severity score (MSSS). Methods: Patients were included from the Danish Multiple Sclerosis Biobank...
October 2018: Multiple Sclerosis Journal—Experimental, Translational and Clinical
Olfat G Shaker, Rania H Mahmoud, Omayma O Abdelaleem, Enas G Ibrahem, Abdelrahmaan A Mohamed, Othman M Zaki, Noha K Abdelghaffar, Tarek I Ahmed, Nada F Hemeda, Naglaa A Ahmed, Dina F Mansour
LncRNAs play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR...
December 4, 2018: Bioscience Reports
Takashi Matsushita
B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β...
November 23, 2018: Journal of Dermatological Science
Jun Eguchi, Kazuya Miyashita, Isamu Fukamachi, Katsuyuki Nakajima, Masami Murakami, Yuko Kawahara, Toru Yamashita, Yasuyuki Ohta, Koji Abe, Atsuko Nakatsuka, Mai Mino, Satoru Takase, Hiroaki Okazaki, Robert A Hegele, Michael Ploug, Xuchen Hu, Jun Wada, Stephen G Young, Anne P Beigneux
BACKGROUND: Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen. OBJECTIVE: A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued...
October 24, 2018: Journal of Clinical Lipidology
Lorna Paul, Linda Renfrew, Jennifer Freeman, Heather Murray, Belinda Weller, Paul Mattison, Alex McConnachie, Robert Heggie, Olivia Wu, Elaine H Coulter
OBJECTIVE: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. DESIGN: Multi-centre, randomized controlled, feasibility study. SETTING: Three multiple sclerosis out-patient centres. PARTICIPANTS: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4-6.5). INTERVENTIONS: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy ( n = 45; intervention) or a sheet of exercises ( n = 45; active comparator)...
December 4, 2018: Clinical Rehabilitation
Ivan Presta, Marco Vismara, Fabiana Novellino, Annalidia Donato, Paolo Zaffino, Elisabetta Scali, Krizia Caterina Pirrone, Maria Francesca Spadea, Natalia Malara, Giuseppe Donato
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system...
December 3, 2018: International Journal of Molecular Sciences
Tonia Woodberry, Sophie E Bouffler, Alicia S Wilson, Rebecca L Buckland, Anne Brüstle
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong autoimmune, neurodegenerative, and neuroinflammatory component. Most of the common disease modifying treatments (DMTs) for MS modulate the immune response targeting disease associated T and B cells and while none directly target neutrophils, several DMTs do impact their abundance or function. The role of neutrophils in MS remains unknown and research is ongoing to better understand the phenotype, function, and contribution of neutrophils to both disease onset and stage of disease...
December 3, 2018: Journal of Clinical Medicine
Drew R Neavin, Duan Liu, Balmiki Ray, Richard M Weinshilboum
The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease-especially for its role in modulating immune and inflammatory responses. AHR has been implicated in many diseases that are driven by immune/inflammatory processes, including major depressive disorder, multiple sclerosis, rheumatoid arthritis, asthma, and allergic responses, among others...
December 3, 2018: International Journal of Molecular Sciences
Anuradha Tarafdar, Giordano Pula
For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation-primarily superoxide anion (O₂●- ), although hydrogen peroxide (H₂O₂) can also be generated...
November 30, 2018: International Journal of Molecular Sciences
Victor M Rivera
Multiple sclerosis (MS) has become a common neurological disorder involving populations previously considered to be infrequently affected. Genetic dissemination from high- to low-risk groups is a determining influence interacting with environmental and epigenetic factors, mostly unidentified. Disease modifying therapies (DMT) are effective in treating relapsing MS in variable degrees; one agent is approved for primary progressive disease, and several are in development. In the era of high-efficacy medications, complex molecules, and monoclonal antibodies (MAB), including anti-VLA4 (natalizumab), anti-CD52 (alemtuzumab), and anti-CD20 (ocrelizumab), obtaining NEDA (no evidence of disease activity) becomes an elusive accomplishment in areas of the world where access to MS therapies and care are generally limited...
November 30, 2018: Biomedicines
M Pisa, P Della Valle, A Coluccia, V Martinelli, G Comi, A D'Angelo, L Moiola
Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Twenty months after the first infusion of alemtuzumab the patient developed acquired haemophilia A (AHA), a treatable but potentially lifethreatening condition that should be considered a possible SADs associated to this drug...
November 29, 2018: Multiple Sclerosis and related Disorders
Laura Negrotto, Jorge Correale
BACKGROUND: Cutaneous adverse effects of Teriflunomide have been rarely reported. OBJECTIVE AND METHODS: We report a relapsing remitting multiple sclerosis patient that developed palmar pustular psoriasis within one month of teriflunomide initiation. RESULTS: Our patient required discontinuation of teriflunomide due to frequent recurrence of pustules with continuous need of local steroid treatment and resolved completely after teriflunomide discontinuation...
November 19, 2018: Multiple Sclerosis and related Disorders
Nira de la Vega Gallardo, Marie Dittmer, Yvonne Dombrowski, Denise C Fitzgerald
Efficient myelin regeneration in the central nervous system (CNS) requires the migration, proliferation and differentiation of oligodendrocyte progenitor cells (OPC) into myelinating oligodendrocytes. In demyelinating diseases such as multiple sclerosis (MS), this regenerative process can fail, and therapies targeting myelin repair are currently completely lacking in the clinic. The immune system is emerging as a key regenerative player in many tissues, such as muscle and heart. We recently reported that regulatory T cells (Treg) are required for efficient CNS remyelination...
December 1, 2018: Neurochemistry International
Juliane Becher, Luca Simula, Elisabetta Volpe, Claudio Procaccini, Claudia La Rocca, Pasquale D'Acunzo, Valentina Cianfanelli, Flavie Strappazzon, Ignazio Caruana, Francesca Nazio, Gerrit Weber, Vincenzo Gigantino, Gerardo Botti, Fabiola Ciccosanti, Giovanna Borsellino, Silvia Campello, Georgia Mandolesi, Marco De Bardi, Gian Maria Fimia, Marcello D'Amelio, Francesca Ruffini, Roberto Furlan, Diego Centonze, Gianvito Martino, Paola Braghetta, Martina Chrisam, Paolo Bonaldo, Giuseppe Matarese, Franco Locatelli, Luca Battistini, Francesco Cecconi
Regulatory T cells (Treg ) are necessary to maintain immunological tolerance and are key players in the control of autoimmune disease susceptibility. Expression of the transcription factor FOXP3 is essential for differentiation of Treg cells and indispensable for their suppressive function. However, there is still a lack of knowledge about the mechanisms underlying its regulation. Here, we demonstrate that pro-autophagy protein AMBRA1 is also a key modulator of T cells, regulating the complex network that leads to human Treg differentiation and maintenance...
December 3, 2018: Developmental Cell
Anne Katrine Andreasen, Pernille Iversen, Lisbet Marstrand, Volkert Siersma, Hartwig Roman Siebner, Finn Sellebjerg
BACKGROUND: Fatigue in multiple sclerosis (MS) is a debilitating symptom and experienced by most patients. In recent studies investigating this phenomenon, the majority of patients had a relapsing-remitting disease course. METHODS: Patients with progressive MS participating in one of three treatment trials during a period from 2010 to 2014 were included. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC) and patients were further examined with a cognitive test battery, including Symbol Digit Modalities Test (SDMT), and 3 T MRI with subsequent quantitative analyses of 13 cortical regions of interest, deep grey matter and lesion volume...
December 4, 2018: Neurological Research
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