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Progressive multiple sclerosis

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https://www.readbyqxmd.com/read/28344997/simple-derivation-of-spinal-motor-neurons-from-escs-ipscs-using-sendai-virus-vectors
#1
Kazuya Goto, Keiko Imamura, Kenichi Komatsu, Kohnosuke Mitani, Kazuhiro Aiba, Norio Nakatsuji, Makoto Inoue, Akihiro Kawata, Hirofumi Yamashita, Ryosuke Takahashi, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons (MNs). Embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) now help us to understand the pathomechanisms of ALS via disease modeling. Various methods to differentiate ESCs/iPSCs into MNs by the addition of signaling molecules have been reported. However, classical methods require multiple steps, and newer simple methods using the transduction of transcription factors run the risk of genomic integration of the vector genes...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28338498/challenge-of-progressive-multiple-sclerosis-therapy
#2
Alan J Thompson
PURPOSE OF REVIEW: Understanding the mechanisms underlying progression in multiple sclerosis (MS) and identifying appropriate therapeutic targets is a key challenge facing the MS community. This challenge has been championed internationally by organizations such as the Progressive MS Alliance, which has raised the profile of progressive MS and identified the key obstacles to treatment. This review will outline the considerable progress against these challenges. RECENT FINDINGS: New insights into mechanisms underlying progression have opened up potential therapeutic opportunities...
March 23, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28334918/adaptive-human-immunity-drives-remyelination-in-a-mouse-model-of-demyelination
#3
Mohamed El Behi, Charles Sanson, Corinne Bachelin, Léna Guillot-Noël, Jennifer Fransson, Bruno Stankoff, Elisabeth Maillart, Nadège Sarrazin, Vincent Guillemot, Hervé Abdi, Isabelle Cournu-Rebeix, Bertrand Fontaine, Violetta Zujovic
One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells...
February 22, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334875/white-matter-changes-in-paediatric-multiple-sclerosis-and-monophasic-demyelinating-disorders
#4
Giulia Longoni, Robert A Brown, Parya MomayyezSiahkal, Colm Elliott, Sridar Narayanan, Amit Bar-Or, Ruth Ann Marrie, E Ann Yeh, Massimo Filippi, Brenda Banwell, Douglas L Arnold
Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28328217/development-of-a-selective-inhibitor-of-protein-arginine-deiminase-2
#5
Aaron Muth, Venkataraman Subramanian, Edward Beaumont, Mitesh Nagar, Philip Kerry, Paul McEwan, Hema Srinath, Kathleen Wanda Clancy, Sangram S Parelkar, Paul R Thompson
Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy...
March 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28328179/effect-of-delayed-release-dimethyl-fumarate-on-no-evidence-of-disease-activity-in-relapsing-remitting-multiple-sclerosis-integrated-analysis-of-the-phase-iii-define-and-confirm-studies
#6
E Havrdova, G Giovannoni, R Gold, R J Fox, L Kappos, J Theodore Phillips, M Okwuokenye, J L Marantz
BACKGROUND AND PURPOSE: Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years...
March 22, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#7
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28321351/bilateral-birdshot-retinochoroiditis-and-retinal-astrocytoma
#8
Sunil Mamtora, Yun Wong, Dugald Bell, Teresa Sandinha
Background. This case highlights the importance of recognising multiple pathologies within the eye which may not necessarily be linked. Both birdshot retinochoroiditis and astrocytoma are rare conditions. The case underlines the need for early identification and treatment of birdshot retinochoroiditis with steroids and disease modifying drugs. Astrocytoma in the absence of tuberous sclerosis is also uncommon. Case Presentation. A 36-year-old male presented with 3-month history of bilateral progressive flashing lights and floaters...
2017: Case Reports in Ophthalmological Medicine
https://www.readbyqxmd.com/read/28320798/interventions-to-improve-the-self-management-support-health-professionals-provide-for-people-with-progressive-neurological-conditions-protocol-for-a-realist-synthesis
#9
Freya Davies, Fiona Wood, Alison Bullock, Carolyn Wallace, Adrian Edwards
INTRODUCTION: Supporting self-management among people with long-term conditions is recognised as an important component of healthcare. Progressive neurological conditions (PNCs), for example, Parkinson's disease and multiple sclerosis are associated with problems such as fatigue and cognitive impairment which may make self-management more challenging. Health professionals may need to develop specific skills in order to provide effective self-management support for these patients. The review aims to develop explanatory theories about how health professional-targeted interventions to improve self-management support provision for people with PNCs operate in different circumstances...
March 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28320766/an-adverse-lipid-profile-and-increased-levels-of-adiposity-significantly-predict-clinical-course-after-a-first-demyelinating-event
#10
Prudence Tettey, Steve Simpson, Bruce Taylor, Anne-Louise Ponsonby, Robyn M Lucas, Terence Dwyer, Karam Kostner, Ingrid Af van der Mei
OBJECTIVE: To investigate the prospective associations between adiposity and lipid-related variables and conversion to multiple sclerosis (MS), time to subsequent relapse and progression in disability. METHODS: A cohort of 279 participants with a first clinical diagnosis of central nervous system demyelination was prospectively followed to 5-year review. Height, weight, waist and hip circumference were measured, and serum samples taken for measurement of lipids and apolipoproteins...
March 20, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28320165/hla-genotype-as-a-marker-of-multiple-sclerosis-prognosis-a-pilot-study
#11
Andreas P Lysandropoulos, Nicolas Mavroudakis, Massimo Pandolfo, Kaoutar El Hafsi, Wim van Hecke, Anke Maertens, Thibo Billiet, Annemie Ribbens
OBJECTIVE: The identification of a biomarker with prognostic value is an unmet need in multiple sclerosis (MS). The objective of this study was to investigate a possible association of HLA genotype with disease status and progression in MS, based on comprehensive and sensitive clinical and magnetic resonance imaging (MRI) parameters to measure disease effects. METHOD: A total of 118 MS patients (79 females, 39 males) underwent HLA typing. Patient MS status was assessed at two time points in a 2-year interval, based on clinical scores (including EDSS, MSSS, T25FW, 9-HPT, SDMT, BVMT, CVLT-II) and MRI evaluations...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320130/spg2-mimicking-multiple-sclerosis-in-a-family-identified-using-next-generation-sequencing
#12
Anna Rubegni, Carla Battisti, Alessandra Tessa, Alfonso Cerase, Stefano Doccini, Alessandro Malandrini, Filippo M Santorelli, Antonio Federico
Several single gene disorders can potentially be overlooked in the differential diagnostic evaluation of patients with multiple sclerosis (MS). Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1. Neurological symptoms are occasionally observed in female carriers of these mutations. Two women - the proposita (Pt1) and her mother (Pt2) - reported walking difficulties since adolescence and showed progressive cognitive decline...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320120/seasonal-variations-of-25-oh-vitamin-d-serum-levels-are-associated-with-clinical-disease-activity-in-multiple-sclerosis-patients
#13
Christina Hartl, Viola Obermeier, Lisa Ann Gerdes, Mathias Brügel, Rüdiger von Kries, Tania Kümpfel
Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320112/multiple-sclerosis-patients-understanding-and-preferences-for-risks-and-benefits-of-disease-modifying-drugs-a-systematic-review
#14
REVIEW
Gurpreet K Reen, Eli Silber, Dawn W Langdon
BACKGROUND: Multiple sclerosis (MS) patients are faced with complex risk-benefit profiles of disease-modifying drugs (DMDs) when making treatment decisions. For effective shared decision-making, MS patients should understand the risks and benefits of DMDs and make treatment decisions based on personal preferences. METHODS: This is an inclusive systematic review to primarily assess current understanding of MS patients for information about DMDs provided during the standard healthcare system...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319650/-monoclonal-antibodies-in-the-treatment-of-ms-emergence-of-b-cell-targeted-therapies
#15
REVIEW
Ai-Lan Nguyen, Melissa Gresle, Tessa Marshall, Helmut Butzkueven, Judith Field
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease modifying therapies have rapidly emerged, including monoclonal antibodies (mAbs) that have provided highly targeted therapies with superior efficacy compared to platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials, and renewed interest in the mechanism of B-cell depleting therapies to ameliorate relapse activity and progression in MS...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319193/stability-and-predictive-value-of-anti-jcv-antibody-index-in-multiple-sclerosis-a-6-year-longitudinal-study
#16
Harald Hegen, Michael Auer, Gabriel Bsteh, Franziska Di Pauli, Tatiana Plavina, Janette Walde, Florian Deisenhammer, Thomas Berger
BACKGROUND: Risk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies. OBJECTIVE: To investigate the longitudinal evolution of anti-JCV antibody index and to determine the predictive value of baseline anti-JCV antibody index for long-term stability of anti-JCV antibody status. METHODS: MS patients from the MS centre of Medical University of Innsbruck, who had serum sampling for a time period of 4-6 years at intervals of 6±3 months, were included in this retrospective, longitudinal study...
2017: PloS One
https://www.readbyqxmd.com/read/28317272/roles-of-ng2-glia-in-ischemic-stroke
#17
REVIEW
Fei-Er Song, Jia-Lv Huang, Si-Han Lin, Shuo Wang, Guo-Fen Ma, Xiao-Ping Tong
Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions...
March 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28303911/comorbidity-in-multiple-sclerosis-implications-for-patient-care
#18
REVIEW
Ruth Ann Marrie
Most efforts aimed at understanding the notable heterogeneity of outcomes in multiple sclerosis (MS) have focused on disease-specific factors, such as symptoms at initial presentation, initial relapse rate, and age at symptom onset. These factors, however, explain relatively little of the heterogeneity of disease outcomes. Owing to the high prevalence of comorbidity in MS and the potential for its prevention or treatment, comorbidity is of rising interest as a factor that could explain the heterogeneity of outcomes...
March 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28302760/-11-c-pbr28-or-18-f-pbr111-detect-white-matter-inflammatory-heterogeneity-in-multiple-sclerosis
#19
Gourab Datta, Alessandro Colasanti, Nicola Kalk, David R Owen, Gregory Scott, Eugenii Ilan A Rabiner, Roger Gunn, Anne Lingford-Hughes, Omar Malik, Olga Ciccarelli, Richard Nicholas, Lei Nie, Marco Battaglini, Nicola De Stefano, Paul Matthews
Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands ((11)C-PBR28 or (18)F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region)...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28302146/relationship-of-acute-axonal-damage-wallerian-degeneration-and-clinical-disability-in-multiple-sclerosis
#20
Shailender Singh, Tobias Dallenga, Anne Winkler, Shanu Roemer, Brigitte Maruschak, Heike Siebert, Wolfgang Brück, Christine Stadelmann
BACKGROUND: Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. METHODS: Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions...
March 17, 2017: Journal of Neuroinflammation
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