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primary progressive multiple sclerosis

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https://www.readbyqxmd.com/read/28338498/challenge-of-progressive-multiple-sclerosis-therapy
#1
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/28320130/spg2-mimicking-multiple-sclerosis-in-a-family-identified-using-next-generation-sequencing
#2
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/28301067/progressive-iron-accumulation-across-multiple-sclerosis-phenotypes-revealed-by-sparse-classification-of-deep-gray-matter
#3
Ahmed M Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan H Wilman
PURPOSE: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. MATERIALS AND METHODS: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls...
March 16, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28298899/decision-making-in-multiple-sclerosis-the-role-of-aversion-to-ambiguity-for-therapeutic-inertia-among-neurologists-discutir-ms
#4
Gustavo Saposnik, Angel P Sempere, Daniel Prefasi, Daniel Selchen, Christian C Ruff, Jorge Maurino, Philippe N Tobler
OBJECTIVES: Limited information is available on physician-related factors influencing therapeutic inertia (TI) in multiple sclerosis (MS). Our aim was to evaluate whether physicians' risk preferences are associated with TI in MS care, by applying concepts from behavioral economics. DESIGN: In this cross-sectional study, participants answered questions regarding the management of 20 MS case scenarios, completed 3 surveys, and 4 experimental paradigms based on behavioral economics...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28294696/cerebrospinal-fluid-mtdna-concentration-is-elevated-in-multiple-sclerosis-disease-and-responds-to-treatment
#5
Cyra E Leurs, Petar Podlesniy, Ramon Trullas, Lisanne Balk, Martijn D Steenwijk, Arjan Malekzadeh, Fredrik Piehl, Bernard Mj Uitdehaag, Joep Killestein, Jack van Horssen, C E Teunissen
BACKGROUND: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. OBJECTIVES: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28283111/is-multiple-sclerosis-a-length-dependent-central-axonopathy-the-case-for-therapeutic-lag-and-the-asynchronous-progressive-ms-hypotheses
#6
REVIEW
Gavin Giovannoni, Gary Cutter, Maria Pia-Sormani, Shibeshih Belachew, Robert Hyde, Harold Koendgen, Volker Knappertz, Davorka Tomic, David Leppert, Robert Herndon, Claudia A M Wheeler-Kingshott, Olga Ciccarelli, David Selwood, Elisabetta Verdun di Cantogno, Ali-Frederic Ben-Amor, Paul Matthews, Daniele Carassiti, David Baker, Klaus Schmierer
Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28273770/transglutaminase-6-is-an-autoantigen-in-progressive-multiple-sclerosis-and-is-upregulated-in-reactive-astrocytes
#7
Massimiliano Cristofanilli, Daniel Gratch, Benjamin Pagano, Kelsey McDermott, Jessie Huang, Jeffrey Jian, Deneb Bates, Saud A Sadiq
BACKGROUND: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. OBJECTIVE: To investigate TGM6 involvement in multiple sclerosis (MS). METHODS: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28272724/-magnetic-resonance-imaging-with-gadolinium-in-the-acute-phase-of-relapses-in-multiple-sclerosis
#8
P Ortiz, J Bareno, L Cabrera, K Rueda, A Rovira
AIM: To describe the factors that are associated with gadolinium enhancement on MRI in patients with multiple sclerosis (MS) and symptoms of relapse. PATIENTS AND METHODS: A retrospective cross-sectional study of patients over 18 years diagnosed with relapsing-remitting MS, secondary progressive and primary progressive from 2009 to 2014, who had a clinical relapse and underwent brain and spinal resonance with gadolinium during the acute phase of the symptoms. RESULTS: Of the 93 patients enrolled, 70% were women, the average age was 37 ± 9...
March 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28247239/effect-of-fingolimod-on-brain-volume-loss-in-patients-with-multiple-sclerosis
#9
REVIEW
Nicola De Stefano, Diego G Silva, Michael H Barnett
Brain atrophy occurs at a faster rate in patients with multiple sclerosis (MS) than in healthy individuals. In three randomized, controlled, phase III trials, fingolimod reduced the annual rate of brain volume loss (BVL) in patients with relapsing MS (RMS) by approximately one-third relative to that in individuals receiving placebo or intramuscular interferon beta-1a. Analysis of brain volume changes during study extensions has shown that this reduced rate of BVL is sustained in patients with RMS receiving fingolimod continuously...
February 28, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28246026/the-novel-nrf2-inducer-tfm-735-ameliorates-experimental-autoimmune-encephalomyelitis-in-mice
#10
Chika Higashi, Atsuko Kawaji, Naoto Tsuda, Makiko Hayashi, Ryota Saito, Yoko Yagishita, Takafumi Suzuki, Akira Uruno, Masaki Nakamura, Kazunari Nakao, Shoji Furusako, Masayuki Yamamoto
The transcription factor NF-E2-related factor 2 (Nrf2) is a key regulator of cellular defense mechanisms against oxidative stress. Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, is characterized by progressive demyelination and neurodegeneration induced by inflammation and oxidative stress. The induction of Nrf2 signaling has been shown to inhibit disease development and progression in the experimental autoimmune encephalomyelitis (EAE) model of MS in mice. In the present study, we performed a high-throughput screening assay using a chimeric construct of the N-terminal portion of Nrf2 fused to LacZ...
February 25, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28241776/the-effectiveness-of-robot-assisted-gait-training-versus-conventional-therapy-on-mobility-in-severely-disabled-progressive-multiple-sclerosis-patients-ragtime-study-protocol-for-a-randomized-controlled-trial
#11
Sofia Straudi, Fabio Manfredini, Nicola Lamberti, Paolo Zamboni, Francesco Bernardi, Giovanna Marchetti, Paolo Pinton, Massimo Bonora, Paola Secchiero, Veronica Tisato, Stefano Volpato, Nino Basaglia
BACKGROUND: Gait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS). Robot-assisted gait training (RAGT) is an effective rehabilitative treatment but evidence of its superiority compared to other options is lacking. Furthermore, the response to rehabilitation is multidimensional, person-specific and possibly involves functional reorganization processes. The aims of this study are: (1) to test the effectiveness on gait speed, mobility, balance, fatigue and QoL of RAGT compared to conventional therapy (CT) in progressive MS and (2) to explore changes of clinical and circulating biomarkers of neural plasticity...
February 27, 2017: Trials
https://www.readbyqxmd.com/read/28241268/long-term-outcomes-after-autologous-hematopoietic-stem-cell-transplantation-for-multiple-sclerosis
#12
Paolo A Muraro, Marcelo Pasquini, Harold L Atkins, James D Bowen, Dominique Farge, Athanasios Fassas, Mark S Freedman, George E Georges, Francesca Gualandi, Nelson Hamerschlak, Eva Havrdova, Vassilios K Kimiskidis, Tomas Kozak, Giovanni L Mancardi, Luca Massacesi, Daniela A Moraes, Richard A Nash, Steven Pavletic, Jian Ouyang, Montserrat Rovira, Albert Saiz, Belinda Simoes, Marek Trnený, Lin Zhu, Manuela Badoglio, Xiaobo Zhong, Maria Pia Sormani, Riccardo Saccardi
Importance: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. Objective: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. Design, Setting, and Participants: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant...
February 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28239937/smoking-does-not-influence-disability-accumulation-in-primary-progressive-multiple-sclerosis
#13
O Javizian, L M Metz, S Deighton, M W Koch
BACKGROUND AND PURPOSE: The modifiable risk factor cigarette smoking has been associated with an increased risk of developing multiple sclerosis (MS) and with disease activity in relapsing-remitting MS. However, less is known about the effect of smoking on disease progression in progressive MS. Here the association between cigarette smoking and disability accumulation in primary progressive MS (PPMS) is investigated. METHODS: Kaplan-Meier survival analyses and Cox proportional hazard modelling were used to investigate the influence of cigarette smoking on the risk of reaching Expanded Disability Status Scale (EDSS) 4 and 6 as well as the time from EDSS 4 to 6 in patients with PPMS...
April 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#14
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28220288/social-cognition-according-to-cognitive-impairment-in-different-clinical-phenotypes-of-multiple-sclerosis
#15
Cecile Dulau, Mathilde Deloire, Helene Diaz, Aurore Saubusse, Julie Charre-Morin, Antoinette Prouteau, Bruno Brochet
The objective of this study is to evaluate the relationship between social cognition (SC) and cognitive impairment in persons with multiple sclerosis (PwMS). A prospective study was conducted in 60 PwMS, 30 with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS) and 15 with primary progressive MS (PPMS), and in healthy subjects (HS). All subjects were assessed by the Bordeaux Social Cognition Evaluation Protocol (PECS-B) (facial emotion recognition, theory of mind, emotional awareness and cognitive and affective alexithymia), by a large neuropsychological battery and by questionnaires (depression and anxiety)...
February 20, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28209373/cost-utility-of-first-line-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#16
Erkki Soini, Jaana Joutseno, Marja-Liisa Sumelahti
PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting)...
February 13, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28205364/altered-neural-mechanisms-of-cognitive-control-in-patients-with-primary-progressive-multiple-sclerosis-an-effective-connectivity-study
#17
Ekaterina Dobryakova, Maria Assunta Rocca, Paola Valsasina, John DeLuca, Massimo Filippi
Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search-based effective connectivity method. Fourteen patients with PPMS and 22 age- and gender-matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition...
February 16, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28185158/outcome-measures-in-clinical-trials-for-multiple-sclerosis
#18
REVIEW
Caspar E P van Munster, Bernard M J Uitdehaag
Due to the heterogeneous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. Therefore, it can be difficult to assess the true efficacy of interventions in clinical trials. In phase III trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale and the relapse rate. Secondary outcome measures in these trials are the number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) of the brain...
March 2017: CNS Drugs
https://www.readbyqxmd.com/read/28178867/the-relationship-between-white-matter-fiber-damage-and-gray-matter-perfusion-in-large-scale-functionally-defined-networks-in-multiple-sclerosis
#19
Ashley Y Ma, Rita C Vitorino, Seyed-Parsa Hojjat, Alannah D Mulholland, Liying Zhang, Liesly Lee, Timothy J Carroll, Charles G Cantrell, Chase R Figley, Richard I Aviv
BACKGROUND: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. OBJECTIVE: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28166789/the-mrz-reaction-in-primary-progressive-multiple-sclerosis
#20
Tilman Hottenrott, Rick Dersch, Benjamin Berger, Sebastian Rauer, Daniela Huzly, Oliver Stich
BACKGROUND: The MRZ reaction (MRZR), composed of the three antibody indices (AI) against measles, rubella and varicella zoster virus and found positive in the majority of relapsing-remitting multiple sclerosis (RRMS) patients, is absent in other inflammatory neurological diseases (OIND). So far, it has been uncertain whether its differential diagnostic promise extends to patients with primary-progressive multiple sclerosis (PPMS). OBJECTIVE: To investigate the prevalence of MRZR in PPMS compared to RRMS and OIND patients...
February 7, 2017: Fluids and Barriers of the CNS
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