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Dongxiao Jiang, Weiping Ju, Xijun Wu, Xia Zhan
BACKGROUND: To date, although great effort has been made to identify biomarkers of multiple sclerosis (MS), it remains unclear whether lysophosphatidic acid (LPA) can be used as a biomarker for MS. METHODS: This study compared the LPA levels in the serum and cerebrospinal fluid (CSF) in patients with MS in relapse versus in remission and investigated the change in LPA levels in MS patients in relapse after treatment. Forty-one patients with relapsing-remitting MS (RRMS) (21 patients in relapse and 20 patients in remission) and 21 patients with non-inflammatory, non-vascular neurological diseases as controls were included in this study...
March 20, 2018: Neurological Research
Lu Wang, Jian Kang, Liangzhong Lim, Yuanyuan Wei, Jianxing Song
TDP-43 inclusions are characterized by a large spectrum of neurodegenerative diseases such as ALS and Alzheimer's. Functionally, TDP-43 is engaged in forming dynamic granules via liquid-liquid phase separation (LLPS), which is now recognized to be a general principle for organizing a variety of cellular membrane-less organelles. TDP-43 is composed of the N-terminal domain (NTD) adopting an ubiquitin-like fold, two RRMs and C-terminal domain (CTD) with the low-complexity (LC) prion-like sequences. Previously, only the CTD was found to undergo LLPS to form dynamic liquid droplets with relatively small numbers and sizes...
March 16, 2018: Biochemical and Biophysical Research Communications
Nooshin Ghadiri, Negaralsadat Emamnia, Mazdak Ganjalikhani-Hakemi, Kamran Ghaedi, Masoud Etemadifar, Mansoor Salehi, Hedayatollah Shirzad, Mohammad Hossein Nasr-Esfahani
BACKGROUND: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS. OBJECTIVES: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS. METHODS: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken...
March 15, 2018: Gene
Asaff Harel, Dylan Sperling, Maria Petracca, Achillefs Ntranos, Ilana Katz-Sand, Stephen Krieger, Fred Lublin, Zichen Wang, Yangbo Liu, Matilde Inglese
OBJECTIVES: The accuracy of 'no evidence of disease activity' (NEDA) in predicting long-term clinical outcome in patients with relapsing remitting multiple sclerosis (RRMS) is unproven, and there is growing evidence that NEDA does not rule out disease worsening. We used diffusion tensor imaging (DTI) to investigate whether ongoing brain microstructural injury occurs in patients with RRMS meeting NEDA criteria. METHODS: We performed a retrospective study to identify patients with RRMS visiting our centre over a 3-month period who had undergone prior longitudinal DTI evaluation at our facility spanning ≥2 years...
March 16, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Nelly Siller, Jens Kuhle, Muthuraman Muthuraman, Christian Barro, Timo Uphaus, Sergiu Groppa, Ludwig Kappos, Frauke Zipp, Stefan Bittner
BACKGROUND: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament - a major component of the neuro-axonal cytoskeleton - is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. OBJECTIVE: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. METHODS: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Laura Gaetano, Dieter A Häring, Ernst-Wilhelm Radue, Nicole Mueller-Lenke, Avinash Thakur, Davorka Tomic, Ludwig Kappos, Till Sprenger
OBJECTIVE: To study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Data were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.5 mg n = 783, fingolimod 1.25 mg n = 799, or placebo n = 773. Percentage change from baseline in dGM and thalamic volumes was evaluated with FMRIB's Integrated Registration & Segmentation Tool; WM, cGM, and VV were evaluated with structural image evaluation using normalization of atrophy cross-sectional version (SIENAX) at months 12 and 24...
March 14, 2018: Neurology
Ahmed M Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan H Wilman
BACKGROUND: Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. PURPOSE: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. STUDY TYPE: Longitudinal (baseline and 2-year follow-up) retrospective study. SUBJECTS: Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects...
March 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
J Vistbakka, M-L Sumelahti, T Lehtimäki, I Elovaara, S Hagman
BACKGROUND: Biomarkers that could be used in early diagnosis of multiple sclerosis (MS), segregation of disease subtypes, and discrimination of the aggressive disease course from the benign one are urgently needed. OBJECTIVE: The aim of this study was to investigate the specificity of circulating microRNAs: miR-191-5p, miR-128-3p, miR-24-3p, and miR-376c-3p in MS and evaluate their association with disease activity and disability progression. METHODS: The expressions of circulating miRNAs were studied in serum of 100 subjects (53 relapsing-remitting (RRMS), 20 primary progressive (PPMS), and 27 controls), using miScript serum miRNA RT-PCR assay techniques...
March 12, 2018: Acta Neurologica Scandinavica
Michael G Dwyer, Jesper Hagemeier, Niels Bergsland, Dana Horakova, Jonathan R Korn, Nasreen Khan, Tomas Uher, Jennie Medin, Diego Silva, Manuela Vaneckova, Eva Kubala Havrdova, Robert Zivadinov
Background: A percent brain volume change (PBVC) cut-off of -0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers. Percent lateral ventricular volume change (PLVVC) is a strong surrogate measure of PBVC, and may be more feasible for atrophy assessment on real-world scans. However, the PLVVC rate corresponding to the established PBVC cut-off of -0...
2018: NeuroImage: Clinical
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for Relapsing-Remitting Multiple Sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. Aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months...
March 10, 2018: Current Medical Research and Opinion
Virginia Devonshire, Richard Phillips, Hilary Wass, Gerald Da Roza, Peter Senior
Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared with subcutaneous interferon-beta-1a, alemtuzumab significantly reduced clinical disease activity and the rate of brain volume loss, and improved disability outcomes in patients with active RRMS who were either treatment naive (CARE-MS I study) or who had an inadequate response (≥ 1 relapse after ≥ 6 months of treatment) to prior therapy (CARE-MS II study)...
March 10, 2018: Journal of Neurology
Stanley L Cohan, Harold Moses, Jonathan Calkwood, Carlo Tornatore, Chris LaGanke, Kyle E Smoot, Venkata Meka, Macaulay Okwuokenye, Christophe Hotermans, Jason P Mendoza, Monica K Mann, Leslie A Meltzer
BACKGROUND: Delayed-release dimethyl fumarate (DMF) may be a therapeutic option for patients with relapsing-remitting multiple sclerosis (RRMS) who are treated with natalizumab and require a change in therapy. However, there is limited information regarding predictors of favorable treatment outcomes in patients switching from natalizumab to DMF. Clinical practices and sequencing protocols vary. Herein, we present the clinical results, including annualized relapse rate (ARR) and risk of relapse, of a phase 4 retrospective observational study of patients with RRMS who switched from natalizumab to DMF in a community practice setting (STRATEGY)...
February 26, 2018: Multiple Sclerosis and related Disorders
Marcus Unterrainer, C Mahler, L Vomacka, S Lindner, J Havla, M Brendel, G Böning, B Ertl-Wagner, T Kümpfel, V M Milenkovic, R Rupprecht, M Kerschensteiner, P Bartenstein, Nathalie L Albert
PURPOSE: Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [18 F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [18 F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI)...
March 9, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Sheng Chen, Juan Zhang, Qi-Bing Liu, Jing-Cong Zhuang, Lei Wu, Yong-Feng Xu, Hong-Fu Li, Zhi-Ying Wu, Bao-Gou Xiao
Background: Multiple sclerosis (MS) is a common central nervous system autoimmune disorder. Increasing number of genome-wide association study (GWAS) analyses hint that MS is strongly associated with genetics. Unfortunately, almost all the GWAS analyses were Caucasian population based. Numbers of risk loci might not be replicated in Chinese MS patients. Hence, we performed a MassArray Assay to genotype the previously reported variants located in the transcription regulation genes in order to elucidate their role in the Chinese MS patients...
March 20, 2018: Chinese Medical Journal
E D'Amico, F Patti, A Zanghì, S Lo Fermo, C G Chisari, M Zappia
BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e...
March 9, 2018: Expert Review of Clinical Pharmacology
Toru Koda, Akiko Namba, Yuji Nakatsuji, Masaaki Niino, Yusei Miyazaki, Tomoyuki Sugimoto, Makoto Kinoshita, Kazushiro Takata, Kazuya Yamashita, Mikito Shimizu, Toshiyuki Fukazawa, Atsushi Kumanogoh, Hideki Mochizuki, Tatsusada Okuno
We previously demonstrated that patients with multiple sclerosis (MS) of high serum Sema4A levels are resistant to IFN-β therapy. To further elucidate the role of serum Sema4A as a biomarker for therapeutic stratification in MS patients, it is important to clarify the efficacy of other disease-modifying drugs (DMD) in those with high serum Sema4A levels. Thus, in this study we investigated whether fingolimod has beneficial effects on MS patients with high Sema4A levels. We retrospectively analyzed annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change in 56 relapsing-remitting multiple sclerosis (RRMS) patients who had been treated with fingolimod, including those who switched from IFN-β therapy...
2018: PloS One
Ester Canto, Noriko Isobe, Alessandro Didonna, Stephen L Hauser, Jorge R Oksenberg
BACKGROUND: Multiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins. METHODS: We developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients...
March 7, 2018: Journal of Neuroinflammation
Zamzam Mahamud, Joachim Burman, Johan Zelano
BACKGROUND: The 2014 ILAE clinical definition of epilepsy allows diagnosis after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Multiple sclerosis (MS) carries an increased risk of epilepsy, but the risk after a first seizure is unknown. We aimed to investigate the risk of epilepsy in patients with MS who had suffered a first seizure. METHODS: We cross-referenced data from the Swedish MS-register with the national patient register for 15810 MS patients and 43635 controls and included 289 MS patients and 222 controls with a first diagnosis of seizure or status epilepticus (SE) without prior epilepsy or presumed symptomatic aetiology...
March 7, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Olga von Bismarck, Theresa Dankowski, Björn Ambrosius, Nicole Hessler, Gisela Antony, Andreas Ziegler, Muna-Miriam Hoshi, Lilian Aly, Felix Luessi, Sergiu Groppa, Luisa Klotz, Sven G Meuth, Björn Tackenberg, Muriel Stoppe, Florian Then Bergh, Hayrettin Tumani, Tania Kümpfel, Martin Stangel, Christoph Heesen, Brigitte Wildemann, Friedemann Paul, Antonios Bayas, Clemens Warnke, Frank Weber, Ralf A Linker, Ulf Ziemann, Uwe K Zettl, Frauke Zipp, Heinz Wiendl, Bernhard Hemmer, Ralf Gold, Anke Salmen
Objective: To assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS. Methods: The German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline characteristics and the prevalence of neuropsychological symptoms...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
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