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primary progressive multiple sclerosis

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https://www.readbyqxmd.com/read/29781383/preferential-spinal-cord-volume-loss-in-primary-progressive-multiple-sclerosis
#1
Charidimos Tsagkas, Stefano Magon, Laura Gaetano, Simon Pezold, Yvonne Naegelin, Michael Amann, Christoph Stippich, Philippe Cattin, Jens Wuerfel, Oliver Bieri, Till Sprenger, Ludwig Kappos, Katrin Parmar
BACKGROUND: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). OBJECTIVE: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. METHODS: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29780609/serum-heat-shock-protein-70-levels-as-a-biomarker-for-inflammatory-processes-in-multiple-sclerosis
#2
Patricia Lechner, Dorothea Buck, Lisa Sick, Bernhard Hemmer, Gabriele Multhoff
Background: Inflammatory and neurodegenerative processes are hallmarks of multiple sclerosis (MS). The synthesis of the major stress-inducible heat shock protein 70 (Hsp70) is induced by inflammation. Objective: The purpose of this study is to determine whether Hsp70 in serum can serve as a potential biomarker to distinguish inflammatory and neurodegenerative processes in MS. Methods: Serum was obtained from 94 patients: 26 clinically isolated syndrome (CIS), 40 relapsing-remitting MS (RRMS), 19 secondary progressive MS (SPMS), and nine primary progressive MS (PPMS)...
April 2018: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29780394/monosodium-urate-crystals-activate-the-inflammasome-in-primary-progressive-multiple-sclerosis
#3
Federica Piancone, Marina Saresella, Ivana Marventano, Francesca La Rosa, Maria Antonia Santangelo, Domenico Caputo, Laura Mendozzi, Marco Rovaris, Mario Clerici
Inflammasome-driven inflammation is postulated to play a role in multiple sclerosis (MS), but there is no direct evidence that the nod-like receptor protein 3 (NLRP3) inflammasome is involved in MS pathogenesis. Uric acid was shown to be one of the "danger" signals involved in the activation of NLRP3 inflammasome; notably, the concentration of uric acid is increased in the serum and in the cerebrospinal fluid of MS individuals. To better investigate the role of the NLRP3 inflammasome in MS-associated inflammation, we primed with lipopolysaccharide and stimulated with monosodium urate crystals PBMCs of 41 MS patients with different disease phenotypes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29775134/csf-inflammatory-biomarkers-responsive-to-treatment-in-progressive-multiple-sclerosis-capture-residual-inflammation-associated-with-axonal-damage
#4
Jeppe Romme Christensen, Mika Komori, Marina Rode von Essen, Rikke Ratzer, Lars Börnsen, Bibi Bielekova, Finn Sellebjerg
BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#5
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29743290/cerebrospinal-fluid-immunoglobulin-light-chain-ratios-predict-disease-progression-in-multiple-sclerosis
#6
Emma Rathbone, Lindsay Durant, James Kinsella, Antony R Parker, Ghaniah Hassan-Smith, Michael R Douglas, S John Curnow
OBJECTIVE: To determine whether the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda light chains at time of multiple sclerosis (MS) diagnosis predicts disease progression and whether this was intrinsic to CSF plasmablasts. METHODS: CSF and peripheral blood were obtained from patients undergoing elective diagnostic lumbar puncture and included clinically isolated syndrome (CIS) (n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease controls, both inflammatory (ONID; n=23) and non-inflammatory (OND; n=114)...
May 9, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29741648/progression-of-regional-grey-matter-atrophy-in-multiple-sclerosis
#7
Arman Eshaghi, Razvan V Marinescu, Alexandra L Young, Nicholas C Firth, Ferran Prados, M Jorge Cardoso, Carmen Tur, Floriana De Angelis, Niamh Cawley, Wallace J Brownlee, Nicola De Stefano, M Laura Stromillo, Marco Battaglini, Serena Ruggieri, Claudio Gasperini, Massimo Filippi, Maria A Rocca, Alex Rovira, Jaume Sastre-Garriga, Jeroen J G Geurts, Hugo Vrenken, Viktor Wottschel, Cyra E Leurs, Bernard Uitdehaag, Lukas Pirpamer, Christian Enzinger, Sebastien Ourselin, Claudia A Gandini Wheeler-Kingshott, Declan Chard, Alan J Thompson, Frederik Barkhof, Daniel C Alexander, Olga Ciccarelli
Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres...
May 8, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29740872/prodromal-symptoms-of-multiple-sclerosis-in-primary-care
#8
Giulio Disanto, Chiara Zecca, Sharon MacLachlan, Rosaria Sacco, Lahiru Handunnetthi, Ute C Meier, Alex Simpson, Laura McDonald, Andrea Rossi, Pascal Benkert, Jens Kuhle, Sreeram V Ramagopalan, Claudio Gobbi
OBJECTIVE: Early diagnosis and treatment initiation significantly influence long term disability outcome in multiple sclerosis (MS). We aimed at identifying prodromal symptoms of MS in primary care settings. METHODS: This was a nested case-control study comparing the occurrence of various symptoms in MS patients vs controls at 0-2, 2-5 and 5-10 years before index date (first MS record). A total of 10,204 incident MS cases were identified within the UK Clinical Practice Research Datalink (CPRD) between 01/01/1987 and 28/02/2016 (median (IQR) age=47 (39-57) years, females=7,308 (71...
May 8, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29737455/current-and-future-use-of-chloroquine-and-hydroxychloroquine-in-infectious-immune-neoplastic-and-neurological-diseases-a-mini-review
#9
REVIEW
Domenico Plantone, Tatiana Koudriavtseva
The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects...
May 8, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29724765/imaging-differences-between-neuromyelitis-optica-spectrum-disorders-and-multiple-sclerosis-a-multi-institutional-study-in-japan
#10
H Tatekawa, S Sakamoto, M Hori, Y Kaichi, A Kunimatsu, K Akazawa, T Miyasaka, H Oba, T Okubo, K Hasuo, K Yamada, T Taoka, S Doishita, T Shimono, Y Miki
BACKGROUND AND PURPOSE: Both clinical and imaging criteria must be met to diagnose neuromyelitis optica spectrum disorders and multiple sclerosis. However, neuromyelitis optica spectrum disorders are often misdiagnosed as MS because of an overlap in MR imaging features. The purpose of this study was to confirm imaging differences between neuromyelitis optica spectrum disorders and MS with visually detailed quantitative analyses of large-sample data. MATERIALS AND METHODS: We retrospectively examined 89 consecutive patients with neuromyelitis optica spectrum disorders (median age, 51 years; range, 16-85 years; females, 77; aquaporin 4 immunoglobulin G-positive, 93%) and 89 with MS (median age, 36 years; range, 18-67 years; females, 68; relapsing-remitting MS, 89%; primary-progressive MS, 7%; secondary-progressive MS, 2%) from 9 institutions across Japan (April 2008 to December 2012)...
May 3, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29719400/new-horizons-for-multiple-sclerosis-therapeutics-milestones-in-the-development-of-ocrelizumab
#11
REVIEW
Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Eleonora Cocco
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system, and both T and B cells are involved in its pathogenesis. The vast majority of disease-modifying drugs used for MS act on the inflammatory component of the disease and are approved for use in relapsing-remitting (RR) patients. Ocrelizumab (OCR) is the only MS drug that has been approved by the US Food and Drug Administration (FDA) not only for patients with RRMS but also for patients with primary progressive (PP) MS...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29695598/preapproval-and-postapproval-evidence-on-drugs-for-multiple-sclerosis
#12
REVIEW
Chiara Gerardi, Vittorio Bertele', Silvia Rossi, Silvio Garattini, Rita Banzi
OBJECTIVE: To review the evidence supporting the European Union marketing authorization of drugs for multiple sclerosis (MS) and assess how far postmarketing research addresses information gaps at the time of approval. METHODS: Through its database, we identified drugs approved by the European Medicines Agency and gathered data on pivotal trials from the European Public Assessment Reports and corresponding publications. We searched Medline, Embase, Cochrane Library, and trial registries for postmarketing randomized controlled trials testing the drugs identified in any form of the disease...
April 25, 2018: Neurology
https://www.readbyqxmd.com/read/29686117/comprehensive-systematic-review-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#13
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms. METHODS: Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29686116/practice-guideline-recommendations-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#14
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29685206/chaos-theory-for-clinical-manifestations-in-multiple-sclerosis
#15
Tetsuya Akaishi, Toshiyuki Takahashi, Ichiro Nakashima
Multiple sclerosis (MS) is a demyelinating disease which characteristically shows repeated relapses and remissions irregularly in the central nervous system. At present, the pathological mechanism of MS is unknown and we do not have any theories or mathematical models to explain its disseminated patterns in time and space. In this paper, we present a new theoretical model from a viewpoint of complex system with chaos model to reproduce and explain the non-linear clinical and pathological manifestations in MS...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29682349/multiple-sclerosis-patients-with-markedly-low-intrathecal-antibody-response-in-sri-lanka
#16
S M K Gamage, I Wijeweera, S B Adikari, Katharina Fink, Jan Hillert, Anna Fogdell-Hahn, H M A Sominanda
Multiple sclerosis (MS) is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis...
2018: Multiple Sclerosis International
https://www.readbyqxmd.com/read/29680179/progress-in-understanding-the-pathophysiology-of-multiple-sclerosis
#17
REVIEW
H Zéphir
Multiple sclerosis (MS) arises in people who have a genetic susceptibility to environmental factors and events, which ultimately trigger the disease. It is thought that peripheral immune cells are mobilized and enter the CNS through the impaired blood-brain barrier in the subarachnoid space, as acute lesions show large numbers of macrophages and CD8+ T cells and, to a lesser extent, CD4+ T cells, B cells and plasma cells. Demyelination is mostly localized to focal lesions in early relapsing-remitting (RR) MS, whereas other areas of white matter appear normal...
April 18, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29673365/human-central-nervous-system-astrocytes-support-survival-and-activation-of-b-cells-implications-for-ms-pathogenesis
#18
Hanane Touil, Antonia Kobert, Nathalie Lebeurrier, Aja Rieger, Philippe Saikali, Caroline Lambert, Lama Fawaz, Craig S Moore, Alexandre Prat, Jennifer Gommerman, Jack P Antel, Yasuto Itoyama, Ichiro Nakashima, Amit Bar-Or
BACKGROUND: The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease...
April 19, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29668399/phase-ii-randomized-controlled-trial-of-constraint-induced-movement-therapy-in-multiple-sclerosis-part-1-effects-on-real-world-function
#19
Victor W Mark, Edward Taub, Gitendra Uswatte, David M Morris, Gary R Cutter, Terrie L Adams, Mary H Bowman, Staci McKay
BACKGROUND: Constraint-Induced Movement therapy (CIMT) has controlled evidence of efficacy for improving real-world paretic limb use in non-progressive physically disabling disorders (stroke, cerebral palsy). OBJECTIVE: This study sought to determine whether this therapy can produce comparable results with a progressive disorder such as multiple sclerosis (MS). We conducted a preliminary phase II randomized controlled trial of CIMT versus a program of complementary and alternative medicine (CAM) treatments for persons with MS, to evaluate their effect on real-world disability...
March 2018: Neurorehabilitation and Neural Repair
https://www.readbyqxmd.com/read/29664341/cervical-cord-t1-weighted-hypointense-lesions-at-mr-imaging-in-multiple-sclerosis-relationship-to-cord-atrophy-and-disability
#20
Paola Valsasina, Mohammed Aboulwafa, Paolo Preziosa, Roberta Messina, Andrea Falini, Giancarlo Comi, Massimo Filippi, Maria A Rocca
Purpose To characterize the spatial distribution of cervical cord T1-weighted hypointense lesions in patients with multiple sclerosis (MS) and analyze their association with cord atrophy and disability. Materials and Methods For this prospective study that took place between 2014 and 2016, 3.0-T high-resolution T1-weighted cervical cord magnetic resonance (MR) images and clinical evaluations were obtained from 82 patients with relapsing-remitting MS (RRMS), 33 patients with secondary progressive MS (SPMS), 25 patients with primary progressive MS (PPMS), and 35 sex-matched healthy control participants...
April 17, 2018: Radiology
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