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https://www.readbyqxmd.com/read/29053884/looking-into-cognitive-impairment-in-primary-progressive-multiple-sclerosis
#1
Maria Petracca, James Sumowski, Michelle Fabian, Aaron Miller, Fred Lublin, Matilde Inglese
BACKGROUND: Cognitive impairment in primary-progressive multiple sclerosis (PP-MS) is correlated with global brain atrophy. Unfortunately, brain volumes computation requires processing resources not widely available in clinical practice. Therefore we decided to test the predictive role of retinal atrophy metrics on cognitive decline, applying them as proxy of grey matter (GM) atrophy in PP-MS. METHODS: Twenty-five PP-MS patients completed the Brief International Cognitive Assessment for MS (BICAMS) and underwent spectral-domain OCT and 3...
October 20, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29053836/long-term-disability-progression-in-primary-progressive-multiple-sclerosis-a-15-year-study
#2
Maria A Rocca, Maria Pia Sormani, Marco Rovaris, Domenico Caputo, Angelo Ghezzi, Enrico Montanari, Antonio Bertolotto, Alice Laroni, Roberto Bergamaschi, Vittorio Martinelli, Giancarlo Comi, Massimo Filippi
Prognostic markers of primary progressive multiple sclerosis evolution are needed. We investigated the added value of magnetic resonance imaging measures of brain and cervical cord damage in predicting long-term clinical worsening of primary progressive multiple sclerosis compared to simple clinical assessment. In 54 patients, conventional and diffusion tensor brain scans and cervical cord T1-weighted scans were acquired at baseline and after 15 months. Clinical evaluation was performed after 5 and 15 years in 49 patients...
September 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053798/in-vivo-characterization-of-cortical-and-white-matter-neuroaxonal-pathology-in-early-multiple-sclerosis
#3
Tobias Granberg, Qiuyun Fan, Constantina Andrada Treaba, Russell Ouellette, Elena Herranz, Gabriel Mangeat, Céline Louapre, Julien Cohen-Adad, Eric C Klawiter, Jacob A Sloane, Caterina Mainero
Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability...
October 10, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053779/cell-based-therapeutic-strategies-for-multiple-sclerosis
#4
Neil J Scolding, Marcelo Pasquini, Stephen C Reingold, Jeffrey A Cohen
The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis...
July 21, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053775/neuroinflammation-and-its-relationship-to-changes-in-brain-volume-and-white-matter-lesions-in-multiple-sclerosis
#5
Gourab Datta, Alessandro Colasanti, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Eline Van Vlierberghe, Wim Van Hecke, Graham Searle, Andre Santos-Ribeiro, Paul M Matthews
Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients...
September 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29051894/a-diagnostic-surprise-primary-hodgkin-s-lymphoma-of-the-lung
#6
Ankur Sinha, Ravikaran Patti, Prabhsimranjot Singh, William Solomon, Yizhak Kupfer
An 81-year-old male presented to the emergency room with a 3-month history of progressive shortness of breath, productive cough with white sputum, and generalized weakness with 10-pound weight loss in 2 months. On presentation, the patient was afebrile, with blood pressure of 93/55 mm Hg and oxy-hemoglobin saturation of 92% on 2 liters of oxygen via nasal cannula. Complete blood count with differential was significant for white count of 12 400/mL. Brain natriuretic peptide level was 454 ng/mL. Postero-anterior chest radiograph showed multiple round opacities in the lung fields...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29050924/-progression-of-nerve-fiber-layer-defects-in-retrobulbar-optic-neuritis-by-the-macular-ganglion-cell-complex
#7
D Hong, C Bosc, F Chiambaretta
INTRODUCTION: Recent studies with SD OCT had shown early axonal damage to the macular ganglion cell complex (which consists of the three innermost layers of the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON), occurring frequently in demyelinating diseases, leads to atrophy of the optic nerve fibers at the level of the ganglion cell axons, previously described in the literature...
October 16, 2017: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/29050818/decreased-serum-levels-of-scd40l-and-il-31-correlate-in-treated-patients-with-relapsing-remitting-multiple-sclerosis
#8
José de J Guerrero-García, Argelia E Rojas-Mayorquín, Yeminia Valle, Jorge R Padilla-Gutiérrez, Víctor A Castañeda-Moreno, Mario A Mireles-Ramírez, José F Muñoz-Valle, Daniel Ortuño-Sahagún
The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS...
October 5, 2017: Immunobiology
https://www.readbyqxmd.com/read/29050389/towards-personalized-therapy-for-multiple-sclerosis-prediction-of-individual-treatment-response
#9
Tomas Kalincik, Ali Manouchehrinia, Lukas Sobisek, Vilija Jokubaitis, Tim Spelman, Dana Horakova, Eva Havrdova, Maria Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Marc Girard, Alexandre Prat, Pierre Duquette, Pierre Grammond, Patrizia Sola, Raymond Hupperts, Francois Grand'Maison, Eugenio Pucci, Cavit Boz, Raed Alroughani, Vincent Van Pesch, Jeannette Lechner-Scott, Murat Terzi, Roberto Bergamaschi, Gerardo Iuliano, Franco Granella, Daniele Spitaleri, Vahid Shaygannejad, Celia Oreja-Guevara, Mark Slee, Radek Ampapa, Freek Verheul, Pamela McCombe, Javier Olascoaga, Maria Pia Amato, Steve Vucic, Suzanne Hodgkinson, Cristina Ramo-Tello, Shlomo Flechter, Edgardo Cristiano, Csilla Rozsa, Fraser Moore, Jose Luis Sanchez-Menoyo, Maria Laura Saladino, Michael Barnett, Jan Hillert, Helmut Butzkueven
Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29049870/dendrimers-breaking-the-paradigm-of-current-musculoskeletal-autoimmune-therapies
#10
REVIEW
Daniel B Rodrigues, Joaquim M Oliveira, Tírcia C Santos, Rui L Reis
The advances achieved by cell-based therapies to treat autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS), despite promising, are still insufficient for the current demands. RA and MS therapeutic approaches follow world guidelines to use disease modifying drugs and biological agents which, regardless of some good results in clinical outcomes, are well known for several systemic secondary side effects. Dendrimers are custom-made nanoparticles with proved clinical potential, displaying proper size, chemistries, immunomodulatory and anti-inflammatory properties...
October 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29045979/-changes-of-serum-krebs-von-den-lungen-6-levels-in-interstitial-lung-disease-associated-with-dermatomyositis-and-secondary-sj%C3%A3-gren-s-syndrome-a-case-report
#11
J F Yu, Y B Jin, J He, Y An, Z G Li
Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. The underlying pathogenesis of ILDs is complex and associated with multiple rheumatologic conditions, such as systemic sclerosis, rheumatoid arthritis, pollymyositis and dermatomyositis, Sjögren's syndrome, and systemic lupus erythematosus. As the disease progresses, excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29045421/enlarged-virchow-robin-spaces-associate-with-cognitive-decline-in-multiple-sclerosis
#12
Alice Favaretto, Andrea Lazzarotto, Alice Riccardi, Stefano Pravato, Monica Margoni, Francesco Causin, Maria Giulia Anglani, Dario Seppi, Davide Poggiali, Paolo Gallo
The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI sequence and investigated their association with inflammation or brain atrophy, and to clinical or physical disability. Forty-three MS patients (21 clinically isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10 healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained with a 3T MRI scanner...
2017: PloS One
https://www.readbyqxmd.com/read/29041873/clinical-trial-design-for-progressive-ms-trials
#13
Matteo Pardini, Gary Cutter, Maria Pia Sormani
The design of clinical trials is a key aspect to maximizing the possibility to detect a treatment effect. This fact is particularly challenging in progressive multiple sclerosis (PMS) studies due to the uncertainty about the right target and/or outcome in phase-2 studies. The aim of this review is to evaluate the current challenges facing the design of clinical trials for PMS. The selection of patients, the instrumental and clinical outcomes that can be used in PMS trials, and issues in their design will be covered in this report...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041872/progressive-ms-trials-lessons-learned
#14
Carmen Tur, Xavier Montalban
Up to very recently, no treatments had proved effective in progressive multiple sclerosis (MS). In 2016, four drugs, two tested in phase 3 and two in phase 2 trials, showed a beneficial effect in primary or secondary progressive MS. Although this could indicate a turning point in progressive MS treatment, most of these successes have been modest and mainly restricted to patients with active inflammation, in the context of trials with powerful anti-inflammatory agents. This paper summarises these reasons, particularly focusing on the main lessons learned for the design of future trials...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041871/advancing-trial-design-in-progressive-multiple-sclerosis
#15
Robert J Fox, Jeremy Chataway
The failure of a majority of clinical trials in progressive multiple sclerosis (MS) has highlighted the need to reconsider how these trials are designed and conducted, and many areas deserve focus. Basic scientists are reconceptualising the pathophysiology of progressive MS into three broad areas: systemic inflammation, compartmentalized inflammation and non-inflammatory neurodegeneration, with the latter two becoming predominant as the disease progresses. This framework will guide the choice of experimental therapies...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041870/fluid-biomarker-and-electrophysiological-outcome-measures-for-progressive-ms-trials
#16
Christian Barro, Letizia Leocani, David Leppert, Giancarlo Comi, Ludwig Kappos, Jens Kuhle
Progressive multiple sclerosis (MS) is characterized by insidious clinical worsening that is difficult to accurately quantify and predict. Biofluid markers and electrophysiological measures are potential candidate outcome measures in clinical trials, allowing the quantification of nervous damage occurring in the disease. Neurofilaments are highly specific neuronal proteins. They may have come closest to such applications by their higher concentrations repeatedly demonstrated in cerebrospinal fluid (CSF) in all stages of MS, during relapses, their responsiveness to disease-modifying treatments in relapsing and progressive MS and their associations with measures of inflammatory and degenerative magnetic resonance imaging (MRI) outcomes...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041869/advancing-trial-design-in-progressive-multiple-sclerosis
#17
David H Miller, Alan J Thompson
No abstract text is available yet for this article.
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041868/the-evolving-role-of-people-with-ms-in-clinical-research-some-progress-but-more-is-needed
#18
Kathryn Smith
People with multiple sclerosis (MS) have been participants in clinical trials over many years, enabling the development and approval of many treatments for relapsing-remitting MS. Today, people with MS expect to be active collaborators in clinical trials and throughout the research and development process. Researchers and clinicians can benefit from including people with MS in all aspects of research and trials, and are urged to do so, so that we can move forward more quickly in developing needed treatments for progressive MS...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041867/patient-selection-for-trials
#19
Jerry S Wolinsky
The last several decades have witnessed considerable progress in our understanding of the pathogenesis, refining diagnostic criteria, and identifying therapies of value for modifying the course of relapsing forms of multiple sclerosis. While the pace of progress has lagged for those with progressive phase disease, this now seems to be changing. This review considers those characteristics of patients with primary progressive multiple sclerosis that may contribute to phase 3 trial success and identifies some of the thorny issues that remain ahead...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041866/-progressive-ms-macro-views-the-need-for-novel-clinical-trial-paradigms-to-enable-drug-development-for-progressive-ms
#20
P Zaratin, G Comi, D Leppert
This article outlines the principal challenges to establish a standard phase-2 approach for progressive multiple sclerosis (PMS) and presents referring strategies to accelerate the registration process via a guidance approved by regulatory agencies. Accordingly, the contribution of 'big datasets' for a better understanding of the natural history of primary-progressive multiple sclerosis (PPMS) and secondary-progressive multiple sclerosis (SPMS) and of their prognostic factors and the value of novel biomarkers are discussed...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
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