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primary progressive multiple sclerosis

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https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#1
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSB) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28928026/an-online-resource-to-promote-vocational-interests-among-job-seekers-with-multiple-sclerosis-a-randomized-controlled-trial-in-australia
#2
Diana Dorstyn, Rachel Roberts, Gregory Murphy, Ian Kneebone, Ashley Craig, Christine Migliorini
OBJECTIVE: To provide a preliminary evaluation of the effectiveness of an on-line resource for job-seekers with multiple sclerosis. DESIGN: Randomized controlled design. SETTING: Community-dwelling cohort in Australia. PARTICIPANTS: Forty-seven adults with relapsing-remitting or progressive MS accessed an email-delivered, 7-module resource - 'Work and MS' - over a 4-week period. Fifty wait-list control participants were offered the opportunity to access 'Work and MS' 4 weeks post-enrolment...
September 16, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28890199/distinct-cognitive-impairments-in-different-disease-courses-of-multiple-sclerosis-a-systematic-review-and-meta-analysis
#3
REVIEW
Andreas Johnen, Nils C Landmeyer, Paul-Christian Bürkner, Heinz Wiendl, Sven G Meuth, Heinz Holling
Cognitive impairment (CI) is common and debilitating in patients with multiple sclerosis. However, little is known about how different disease courses affect CI, impeding prognosis and disease management. Here, we contrasted the magnitude and profile of CI measured with standardized neuropsychological tests in patients with primary progressive multiple sclerosis (PPMS) against relapsing-remitting multiple sclerosis (RRMS) while considering potentially confounding demographic and clinical differences. Systematic literature review and meta-analysis was performed finding 47 eligible studies (N=4460 patients)...
September 8, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28871238/overcoming-therapeutic-inertia-in-multiple-sclerosis-care-a-pilot-randomized-trial-applying-the-traffic-light-system-in-medical-education
#4
Gustavo Saposnik, Jorge Maurino, Angel P Sempere, Maria A Terzaghi, Christian C Ruff, Muhammad Mamdani, Philippe N Tobler, Xavier Montalban
BACKGROUND: Physicians often do not initiate or intensify treatments when clearly warranted, a phenomenon known as therapeutic inertia (TI). Limited information is available on educational interventions to ameliorate knowledge-to-action gaps in TI. OBJECTIVES: To evaluate the feasibility and efficacy of an educational intervention compared to usual care among practicing neurologists caring for patients with multiple sclerosis (MS). METHODS: We conducted a pilot double-blind, parallel-group, randomized clinical trial...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28870585/medical-decision-making-capacity-and-its-cognitive-predictors-in-progressive-ms-preliminary-evidence
#5
Adam Gerstenecker, Kathleen Lowry, Terina Myers, Khurram Bashir, Kristen L Triebel, Roy C Martin, Daniel C Marson
BACKGROUND: Medical decision-making capacity (MDC) refers to the ability to make informed decisions about treatment and declines in cognition are associated with declines in MDC across multiple disease entities. However, although it is well known that cognitive impairment is prevalent in multiple sclerosis (MS), little is known about MDC in the disease. METHODS: Data from 22 persons with progressive MS and 18 healthy controls were analyzed. All diagnoses were made by a board-certified neurologist with experience in MS...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28870573/cxcl10-and-cxcl13-chemokines-in-patients-with-relapsing-remitting-and-primary-progressive-multiple-sclerosis
#6
Piotr Iwanowski, Jacek Losy, Lucyna Kramer, Marlena Wójcicka, Elżbieta Kaufman
OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by a variable clinical course. Different pathogenic mechanisms responsible for relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS) are modulated by immunological process with important role of chemokine network. CXCL10 and CXCL13 chemokines act as chemoattractants and modulators of proinflammatory reactions promoting process of demyelination...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28868516/analysis-of-human-endogenous-retrovirus-expression-in-multiple-sclerosis-plaques
#7
P J Bhetariya, J D Kriesel, K F Fischer
BACKGROUND: It has been suggested that Human endogenous retroviruses (HERVs) are associated with multiple sclerosis (MS) pathogenesis. The objective of this study was to broadly evaluate the expression of HERV core (GAG) and envelope (ENV) genes in diseased brain white matter samples from MS patients compared to normal controls. METHODS: Twenty-eight HERV GAG and 88 ENV gene sequences were retrieved, classified by phylogeny, and grouped into clades. Consensus qPCR primers were designed for each clade, and quantitative PCR was performed on 33 MS and 9 normal control frozen brain samples...
August 2017: J Emerg Dis Virol
https://www.readbyqxmd.com/read/28861122/the-role-of-natalizumab-in-the-treatment-of-multiple-sclerosis-benefits-and-risks
#8
REVIEW
Barry A Singer
Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the central nervous system, is a valuable tool in the treatment of relapsing forms of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 12-week confirmed disability progression by 42%, and reduced contrast-enhancing lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 37% of patients achieving no evidence of disease activity (versus 7% on placebo) and 30% achieving sustained disability improvement (versus 19% on placebo)...
September 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28832890/the-gulf-war-era-multiple-sclerosis-cohort-3-early-clinical-features
#9
M T Wallin, W J Culpepper, H Maloni, J F Kurtzke
OBJECTIVES: To present clinical features at diagnosis for a large nationwide incident cohort of multiple sclerosis (MS) among those serving in the US military during the Gulf War era (GWE). MATERIALS & METHODS: Medical records and databases from the Department of Veterans Affairs (VA) for cases of MS with onset in or after 1990, active duty between 1990 and 2007 and service connection by the VA, were reviewed for diagnosis and demographic variables. Neurological involvement was summarized by the Kurtzke Disability Status Scale (DSS) and the Multiple Sclerosis Severity Score (MSSS)...
August 22, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28831853/defining-active-progressive-multiple-sclerosis
#10
Finn Sellebjerg, Lars Börnsen, Cecilie Ammitzbøll, Jørgen Erik Nielsen, Tua Vinther-Jensen, Lena Elisabeth Hjermind, Marina von Essen, Rikke Lenhard Ratzer, Per Soelberg Sørensen, Jeppe Romme Christensen
BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria. METHODS: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24)...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28812249/long-term-disability-and-progression-in-spinal-onset-multiple-sclerosis
#11
Bedile Irem Tiftikcioglu, Irem Ilgezdi, Yasar Zorlu, Ufuk Sener, Figen Tokucoglu
The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12 months. Eventually, 476 MS patients were included...
August 10, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28797088/csf-profile-in-primary-progressive-multiple-sclerosis-re-exploring-the-basics
#12
Ahmed Abdelhak, Tilman Hottenrott, Christoph Mayer, Gudrun Hintereder, Uwe K Zettl, Oliver Stich, Hayrettin Tumani
OBJECTIVE: The aim of this study was to report the basic cerebrospinal fluid (CSF) profile in patients with primary progressive multiple sclerosis (PPMS). METHODS: The results of CSF analysis from 254 patients with PPMS were collected at four university hospitals in Germany. Routine CSF parameters and different indices of intrathecal immunoglobulin synthesis were evaluated. We assessed possible correlations between the various CSF parameters and the expanded disability status scale (EDSS) both at the time of lumbar puncture and during the course of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28794971/the-relationship-between-cortical-lesions-and-periventricular-nawm-abnormalities-suggests-a-shared-mechanism-of-injury-in-primary-progressive-ms
#13
Matteo Pardini, Maria Petracca, Asaff Harel, Lazar Fleysher, Niels Oesingmann, Giulia Bommarito, Michelle Fabian, Declan Chard, Fred Lublin, Matilde Inglese
In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28793296/older-age-at-multiple-sclerosis-onset-is-an-independent-factor-of-poor-prognosis-a-population-based-cohort-study
#14
Francis Guillemin, Cédric Baumann, Jonathan Epstein, Philippe Kerschen, Teresa Garot, Guillaume Mathey, Marc Debouverie
BACKGROUND: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. METHODS: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling...
August 10, 2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28792103/progression-of-regional-atrophy-in-the-left-hemisphere-contributes-to-clinical-and-cognitive-deterioration-in-multiple-sclerosis-a-5-year-study
#15
Paolo Preziosa, Elisabetta Pagani, Sarlota Mesaros, Gianna C Riccitelli, Jelena Dackovic, Jelena Drulovic, Massimo Filippi, Maria A Rocca
In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls...
August 9, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28791401/implications-of-white-matter-damage-in-amyotrophic-lateral-sclerosis-review
#16
Ting Zhou, Tina Khorshid Ahmad, Kiana Gozda, Jessica Truong, Jiming Kong, Michael Namaka
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal‑glial interactions...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28780745/effectiveness-and-safety-of-dimethyl-fumurate-treatment-in-relapsing-multiple-sclerosis-patients-a-real-world-evidence
#17
Raed Alroughani, Samar Farouk Ahmed, Raed Behbehani, Jasem Al-Hashel
INTRODUCTION: Dimethyl fumurate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials. OBJECTIVE: To evaluate effectiveness and safety of DMF and to measure the occurrence of lymphopenia in a cohort of MS patients in a clinical setting. METHODS: Using the national MS registry, we prospectively assessed relapsing MS patients who had been prescribed DMF for at least 6 months...
August 5, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28777826/cerebrospinal-fluid-b-cells-and-disease-progression-in-multiple-sclerosis-a-longitudinal-prospective-study
#18
Sebastian Wurth, Bettina Kuenz, Gabriel Bsteh, Rainer Ehling, Franziska Di Pauli, Harald Hegen, Michael Auer, Viktoria Gredler, Florian Deisenhammer, Markus Reindl, Thomas Berger
BACKGROUND: There is evidence that B cells play an important role in disease pathology of multiple sclerosis (MS). The aim of this prospective observational study was to determine the predictive value of cerebrospinal fluid (CSF) B cell subtypes in disease evolution of patients with MS. MATERIALS AND METHODS: 128 patients were included between 2004 and 2012. Median follow up time was 7.9 years (range 3.3-10.8 years). 10 patients were lost to follow-up. 32 clinically isolated syndrome- (CIS), 25 relapsing remitting MS- (RRMS), 2 secondary progressive MS- (SPMS) and 9 primary progressive MS- (PPMS) patients were included...
2017: PloS One
https://www.readbyqxmd.com/read/28746432/late-onset-multiple-sclerosis-concerns-in-aging-patients
#19
Claudia Beatriz de Campos Lotti, Acary Souza Bulle Oliveira, Denis Bernardi Bichuetti, Isac de Castro, Enedina Maria Lobato Oliveira
Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50 years of age, representing 4.5% of multiple sclerosis (MS) patients. This study describes the clinical characteristics of patients with LOMS followed at a specialized MS center in São Paulo. Data was obtained from medical records of 742 patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years and the predominant disease course was primary progressive (64.3%). The patients reached the disability landmarks of EDSS grades 3...
July 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/28744195/machine-learning-approach-for-classifying-multiple-sclerosis-courses-by-combining-clinical-data-with-lesion-loads-and-magnetic-resonance-metabolic-features
#20
Adrian Ion-Mărgineanu, Gabriel Kocevar, Claudio Stamile, Diana M Sima, Françoise Durand-Dubief, Sabine Van Huffel, Dominique Sappey-Marinier
Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e...
2017: Frontiers in Neuroscience
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