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https://www.readbyqxmd.com/read/28917696/brain-mapping-in-multiple-sclerosis-lessons-learned-about-the-human-brain
#1
REVIEW
Massimo Filippi, Paolo Preziosa, Maria A Rocca
The application of structural and functional magnetic resonance imaging (MRI) techniques in patients with multiple sclerosis (MS) has certainly helped to improve our understanding of the mechanisms responsible for clinical disability and cognitive impairment in this condition. The numerous studies performed in MS patients have also provided many lessons on the structure-function relationships in the human brain, which could be applied to healthy subjects and to patients affected by other neurological conditions...
September 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28916537/reversibility-of-the-effects-of-natalizumab-on-peripheral-immune-cell-dynamics-in-ms-patients
#2
Tatiana Plavina, Kumar Kandadi Muralidharan, Geoffrey Kuesters, Daniel Mikol, Karleyton Evans, Meena Subramanyam, Ivan Nestorov, Yi Chen, Qunming Dong, Pei-Ran Ho, Diogo Amarante, Alison Adams, Jerome De Sèze, Robert Fox, Ralf Gold, Douglas Jeffery, Ludwig Kappos, Xavier Montalban, Bianca Weinstock-Guttman, Hans-Peter Hartung, Bruce A C Cree
OBJECTIVE: To characterize the reversibility of natalizumab-mediated changes in pharmacokinetics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. METHODS: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) studies...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28914581/circulating-lymphocyte-levels-and-relationship-with-infection-status-in-patients-with-relapsing-remitting-multiple-sclerosis-treated-with-daclizumab-beta
#3
Gavin Giovannoni, Heinz Wiendl, Benjamin Turner, Kimberly Umans, Oksana Mokliatchouk, Wanda Castro-Borrero, Steven J Greenberg, Peter McCroskery, Giorgio Giannattasio
BACKGROUND: Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. OBJECTIVE: To analyse total and differential lymphocyte levels and relationship with infection status. METHODS: In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4(+)/CD8(+) T-cell counts...
September 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28914385/multiple-sclerosis-and-rehabilitation-an-overview-of-the-different-rehabilitation-settings
#4
Andrea Tacchino, Giampaolo Brichetto, Paola Zaratin, Mario Alberto Battaglia, Michela Ponzio
To date, a lack of accurate information about how the different rehabilitation settings are actually delivered to people with multiple sclerosis (PwMS) is still present. Here, we described how PwMS use the different rehabilitation settings in Italy. An observational retrospective study was designed and data collected through an anonymous questionnaire distributed attending MS clinical centers, rehabilitation units, or among PwMS affiliated to the Italian MS Society. We considered as settings: out-patient ambulatory therapy (OUT), hospitalized therapy (HOSP, in-patient and out-patient hospitalized therapy), and home-based therapy (HOME)...
September 15, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28914229/clinical-effectiveness-and-cost-effectiveness-of-beta-interferon-and-glatiramer-acetate-for-treating-multiple-sclerosis-systematic-review-and-economic-evaluation
#5
G J Melendez-Torres, Peter Auguste, Xavier Armoiry, Hendramoorthy Maheswaran, Rachel Court, Jason Madan, Alan Kan, Stephanie Lin, Carl Counsell, Jacoby Patterson, Jeremy Rodrigues, Olga Ciccarelli, Hannah Fraser, Aileen Clarke
BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28913826/modeling-tolerance-development-for-the-effect-on-heart-rate-of-the-selective-s1p1-receptor-modulator-ponesimod
#6
Dominik Lott, Thorsten Lehr, Jasper Dingemanse, Andreas Krause
Ponesimod is a selective sphingosine-1-phosphate-1 (S1P1 ) receptor modulator currently under investigation for the treatment of multiple sclerosis. S1P receptor modulators reduce heart rate following treatment initiation. This effect disappears with repeated dosing, enabling development of innovative up-titration regimens to optimize patient safety. There are currently no published pharmacokinetic/pharmacodynamic models describing the heart rate reduction of S1P receptor modulators in humans. The model developed here provides quantification of this effect for ponesimod...
September 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28913819/emergency-neurologic-life-support-spinal-cord-compression
#7
Kristine H O'Phelan
There are many causes of acute myelopathy including multiple sclerosis, systemic disease, and acute spinal cord compression (SCC). SCC should be among the first potential causes considered given the significant permanent loss of neurologic function commonly associated with SCC. This impairment can occur over a short period of time, and may be avoided through rapid and acute surgical intervention. Patients with SCC typically present with a combination of motor and sensory dysfunction that has a distribution referable to a spinal level...
September 14, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28913785/evolution-of-patient-reported-outcomes-and-their-role-in-multiple-sclerosis-clinical-trials
#8
REVIEW
Cindy J Nowinski, Deborah M Miller, David Cella
Patient-reported outcomes (PROs) are playing an increasing role in multiple sclerosis (MS) research and practice, and are essential for understanding the effects that MS and MS treatments have on patients' lives. PROs are captured directly from patients and include symptoms, function, health status, and health-related quality of life. In this article, we review different categories (e.g., generic, targeted, preference-based) of PRO measures and considerations in selecting a measure. The PROs included in MS clinical research have evolved over time, as have the measures used to assess them...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#9
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913726/diagnosis-and-treatment-of-progressive-multifocal-leukoencephalopathy-associated-with-multiple-sclerosis-therapies
#10
REVIEW
Eric M L Williamson, Joseph R Berger
Progressive multifocal leukoencephalopathy (PML) is a rare, but serious, complication encountered in patients treated with a select number of disease-modifying therapies (DMTs) utilized in treating multiple sclerosis (MS). PML results from a viral infection in the brain for which the only demonstrated effective therapy is restoring the perturbed immune system-typically achieved in the patient with MS by removing the offending therapeutic agent or, in the case of HIV-associated PML, treatment with highly active antiretroviral therapies...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#11
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28911655/therapeutic-effects-of-d-aspartate-in-a-mouse-model-of-multiple-sclerosis
#12
Sanaz Afraei, Antimo D'Aniello, Reza Sedaghat, Parvin Ekhtiari, Gholamreza Azizi, Nakisa Tabrizian, Laura Magliozzi, Zahra Aghazadeh, Abbas Mirshafiey
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp) on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55) in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28911260/two-year-results-from-a-phase-2-extension-study-of-oral-amiselimod-in-relapsing-multiple-sclerosis
#13
Ludwig Kappos, Douglas L Arnold, Amit Bar-Or, A John Camm, Tobias Derfuss, Till Sprenger, Martin Davies, Alexandra Piotrowska, Pingping Ni, Tomohiko Harada
BACKGROUND: Amiselimod, an oral selective sphingosine-1-phosphate 1 receptor modulator, suppressed disease activity dose-dependently without clinically relevant bradyarrhythmia in a 24-week phase 2, placebo-controlled study in relapsing-remitting multiple sclerosis. OBJECTIVE: To assess safety and efficacy of amiselimod over 96 weeks. METHODS: After completing the core study, patients on amiselimod continued at the same dose, whereas those on placebo were randomised 1:1:1 to amiselimod 0...
September 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28910968/efficiency-of-antibody-therapy-in-demyelinating-diseases
#14
Tetsuya Akaishi, Ichiro Nakashima
Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28906152/relapse-outcomes-safety-and-treatment-patterns-in-patients-diagnosed-with-relapsing-remitting-multiple-sclerosis-and-initiated-on-subcutaneous-interferon-%C3%AE-1a-or-dimethyl-fumarate-a-real-world-study
#15
Frank R Ernst, Peri Barr, Riad Elmor, Schiffon L Wong
OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif®) versus dimethyl fumarate (DMF; Tecfidera(®)), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A U.S. retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF...
September 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#16
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
September 14, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28905370/neuromodulation-and-devices-in-trigeminal-neuralgia
#17
Kevin Weber
PREMISE: Trigeminal neuralgia is a severe facial pain disorder that has been studied for decades. Classical trigeminal neuralgia (CTN) is either idiopathic or caused by neurovascular compression. The related painful trigeminal neuropathies are often secondary to other causes, such as multiple sclerosis or trauma. PROBLEM: Therapies for trigeminal neuralgia and neuropathy have often been pharmacologic or surgical. Pharmacologic therapies are not effective in some cases and often cause side effects, some substantial...
September 14, 2017: Headache
https://www.readbyqxmd.com/read/28905255/benefit-risk-profile-of-sphingosine-1-phosphate-receptor-modulators-in-relapsing-and-secondary-progressive-multiple-sclerosis
#18
Giancarlo Comi, Hans-Peter Hartung, Rajesh Bakshi, Ian M Williams, Heinz Wiendl
Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit-risk profiles are suitable for long-term therapy...
September 13, 2017: Drugs
https://www.readbyqxmd.com/read/28905149/interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma-on-neuroinflammation-demyelination-and-remyelination-in-multiple-sclerosis
#19
REVIEW
Alexandre Vallée, Jean-Noël Vallée, Rémy Guillevin, Yves Lecarpentier
Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation...
September 13, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28903961/paediatric-optic-neuritis-factors-leading-to-unfavourable-outcome-and-relapses
#20
Delphine Averseng-Peaureaux, Marie Mizzi, Helene Colineaux, Laurence Mahieu, Maria Carmela Pera, David Brassat, Yves Chaix, Emilie Berard, Kumaran Deiva, Emmanuel Cheuret
OBJECTIVES: To identify prognostic factors associated with poor visual recovery and chronic relapsing diseases, for example, multiple sclerosis (MS), in children with optic neuritis (ON) at onset. METHODS: This multicentre retrospective study included 102 children with a first ON episode between 1990 and 2012. The primary criterion was poor visual recovery determined by visual acuity, and the secondary was relapses following ON. RESULTS: Median age was 11 years, 66% were girls and mean follow-up was 24 months...
September 13, 2017: British Journal of Ophthalmology
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