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Multiple sclerosis biomarkers

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
Menuka Pallebage-Gamarallage, Sean Foxley, Ricarda A L Menke, Istvan N Huszar, Mark Jenkinson, Benjamin C Tendler, Chaoyue Wang, Saad Jbabdi, Martin R Turner, Karla L Miller, Olaf Ansorge
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically...
March 13, 2018: BMC Neuroscience
Fatma M Mahmoud, Nadia M ElSheshtawy, Wafaa K Zaki, Dina M Zamzam, Nehal M Fahim
Multiple sclerosis (MS) is a chronic multifocal inflammatory demyelinating disease. One of the main cells that play a crucial role in pathogenesis of MS is T helper 17 (Th 17). There are growing interests in nominating microRNAs in Th17 cell differentiation and suggesting new therapeutic modalities. The aim of the study was to assess microRNA 26a (miR26a) expression in peripheral blood mononuclear cells of relapsing - remitting MS patients as compared to healthy control subjects and examine association of these levels with serum IL17...
June 2017: Egyptian Journal of Immunology
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
R Magliozzi, O W Howell, R Nicholas, C Cruciani, M Castellaro, C Romualdi, S Rossi, M Pitteri, M D Benedetti, A Gajofatto, F B Pizzini, S Montemezzi, S Rasia, R Capra, A Bertoldo, F Facchiano, S Monaco, R Reynolds, M Calabrese
OBJECTIVE: Grey matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in Multiple Sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS: To identify possible biomarkers linking meningeal inflammation, GM damage and disease severity, gene and protein expression were analysed in meninges and CSF from 27 post-mortem secondary progressive MS (SPMS) and 14 control cases...
March 8, 2018: Annals of Neurology
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
Kofi Deh, Gerald D Ponath, Zaki Molvi, Gian-Carlo T Parel, Kelly M Gillen, Shun Zhang, Thanh D Nguyen, Pascal Spincemaille, Yinghua Ma, Ajay Gupta, Susan A Gauthier, David Pitt, Yi Wang
BACKGROUND: The pathological processes in the first weeks of multiple sclerosis (MS) lesion formation include myelin digestion that breaks chemical bonds in myelin lipid layers. This can increase lesion magnetic susceptibility, which is a potentially useful biomarker in MS patient management, but not yet investigated. PURPOSE: To understand and quantify the effects of myelin digestion on quantitative susceptibility mapping (QSM) of MS lesions. STUDY TYPE: Histological and QSM analyses on in vitro models of myelin breakdown and MS lesion formation in vivo...
March 8, 2018: Journal of Magnetic Resonance Imaging: JMRI
Kelly M Gillen, Mayyan Mubarak, Thanh D Nguyen, David Pitt
Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i...
2018: Frontiers in Immunology
Ida Manna, Enrico Iaccino, Vincenzo Dattilo, Stefania Barone, Eleonora Vecchio, Selena Mimmi, Enrica Filippelli, Giulio Demonte, Serena Polidoro, Alfredo Granata, Sara Scannapieco, Ileana Quinto, Paola Valentino, Aldo Quattrone
Multiple sclerosis (MS) is an autoimmune pathology leading to neurodegeneration. Because of the complexity and heterogenic etiology of this disease, diagnosis and treatment for individual patients are challenging. Exosome-associated microRNAs (miRNAs) have recently emerged as a new class of diagnostic biomarkers involved in both autoimmune and neurologic disorders. Interesting new evidence has emerged showing that circulating miRNAs are dysregulated in MS body fluids, including serum, plasma, and cerebrospinal fluid...
March 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Amit Katiyar, Sujata Sharma, Tej P Singh, Punit Kaur
Women with endometriosis (EMS) appear to be at a higher risk of developing other autoimmune diseases predominantly multiple sclerosis (MS). Though EMS and MS are evidently diverse in their phenotype, they are linked by a common autoimmune condition or immunodeficiency which could play a role in the expansion of endometriosis and possibly increase the risk of developing MS in women with EMS. However, the common molecular links connecting EMS with MS are still unclear. We conducted a meta-analysis of microarray experiments focused on EMS and MS with their respective controls...
2018: Frontiers in Genetics
Anu Paul, Manuel Comabella, Roopali Gandhi
Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease with a complex clinical course characterized by inflammation, demyelination, and axonal degeneration. Diagnosis of MS most commonly includes finding lesions in at least two separate areas of the central nervous system (CNS), including the brain, spinal cord, and optic nerves. In recent years, there has been a remarkable increase in the number of available treatments for MS. An optimal treatment is usually based on a personalized approach determined by an individual patient's prognosis and treatment risks...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
J D Dworkin, K A Linn, I Oguz, G M Fleishman, R Bakshi, G Nair, P A Calabresi, R G Henry, J Oh, N Papinutto, D Pelletier, W Rooney, W Stern, N L Sicotte, D S Reich, R T Shinohara
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location...
February 22, 2018: AJNR. American Journal of Neuroradiology
Clare Baecher-Allan, Belinda J Kaskow, Howard L Weiner
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system...
February 21, 2018: Neuron
John J Chen, W Oliver Tobin, Masoud Majed, Jiraporn Jitprapaikulsan, James P Fryer, Jacqueline A Leavitt, Eoin P Flanagan, Andrew McKeon, Sean J Pittock
Importance: Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) are recently established biomarkers of autoimmune optic neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well-known randomized clinical trial in optic neuritis; therefore, knowledge of the serostatus and accompanying phenotype of these patients would be useful to determine the frequency of these antibodies in patients presenting with typical monocular optic neuritis and their outcomes...
February 22, 2018: JAMA Ophthalmology
Alessandro Serra, Clara G Chisari, Manuela Matta
Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients' disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease...
2018: Frontiers in Neurology
Radhika Raheja, Keren Regev, Brian C Healy, Maria Antonietta Mazzola, Vanessa Beynon, Felipe von Glehn, Anu Paul, Camilo Diaz-Cruz, Taha Gholipour, Bonnie I Glanz, Pia Kivisakk, Tanuja Chitnis, Howard L Weiner, James D Berry, Roopali Gandhi
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a debilitating neurologic disorder with poor survival rates and no clear biomarkers for disease diagnosis and prognosis. METHODS: We compared serum miRNA expression from patients with ALS to healthy controls and patients with multiple sclerosis and Alzheimer's disease. We also correlated miRNA expression in cross-sectional and longitudinal cohorts of ALS patients with clinical parameters. RESULTS: We identified 7 microRNAs (miR-192-5p, miR-192-3p, miR-1, miR-133a-3p, miR-133b, miR-144-5p and miR-19a-3p) that were upregulated and 6 microRNAs (miR-320c, miR-320a, let-7d-3p, miR-425-5p, miR-320b and miR-139-5p) that were downregulated in ALS patients compared to healthy controls, Alzheimer's disease and multiple sclerosis patients...
February 21, 2018: Muscle & Nerve
Kristina M Harris, Tingting Lu, Noha Lim, Laurence A Turka
Autoimmunity represents a broad category of diseases that involve a variety of organ targets and distinct autoantigens. For patients with autoimmune diseases who fail to respond to approved disease-modifying treatments, autologous hematopoietic stem cell transplantation (AHSCT) after high-dose immunosuppressive therapy provides an alternative strategy. Although more than 100 studies have been published on AHSCT efficacy in autoimmunity, the mechanisms that confer long-term disease remission as opposed to continued deterioration or disease reactivation remain to be determined...
2018: Frontiers in Immunology
Keita Takahashi, Hideyuki Takeuchi, Yuji Kurihara, Hiroshi Doi, Misako Kunii, Kenichi Tanaka, Haruko Nakamura, Ryoko Fukai, Atsuko Tomita-Katsumoto, Mikiko Tada, Yuichi Higashiyama, Hideto Joki, Shigeru Koyano, Kohtaro Takei, Fumiaki Tanaka
BACKGROUND: Although inflammation in the central nervous system is responsible for multiple neurological diseases, the lack of appropriate biomarkers makes it difficult to evaluate inflammatory activities in these diseases. Therefore, a new biomarker reflecting neuroinflammation is required for accurate diagnosis, appropriate therapy, and comprehension of pathogenesis of these neurological disorders. We previously reported that the cerebrospinal fluid (CSF) concentration of lateral olfactory tract usher substance (LOTUS), which promotes axonal growth as a Nogo receptor 1 antagonist, negatively correlates with disease activity in multiple sclerosis, suggesting that variation in LOTUS reflects the inflammatory activities and is a useful biomarker to evaluate the disease activity...
February 17, 2018: Journal of Neuroinflammation
Clara Matute-Blanch, Luisa M Villar, José C Álvarez-Cermeño, Konrad Rejdak, Evgeniy Evdoshenko, Gleb Makshakov, Vladimir Nazarov, Sergey Lapin, Luciana Midaglia, Angela Vidal-Jordana, Jelena Drulovic, Antonio García-Merino, Antonio J Sánchez-López, Eva Havrdova, Albert Saiz, Sara Llufriu, Roberto Alvarez-Lafuente, Ina Schroeder, Uwe K Zettl, Daniela Galimberti, Lluís Ramió-Torrentà, René Robles, Ester Quintana, Harald Hegen, Florian Deisenhammer, Jordi Río, Mar Tintoré, Alex Sánchez, Xavier Montalban, Manuel Comabella
The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay...
February 14, 2018: Brain: a Journal of Neurology
George D Vavougios, Triantafyllos Doskas, Kostas Konstantopoulos
Dysarthrophonia is a predominant symptom in many neurological diseases, affecting the quality of life of the patients. In this study, we produced a discriminant function equation that can differentiate MS patients from healthy controls, using electroglottographic variables not analyzed in a previous study. We applied stepwise linear discriminant function analysis in order to produce a function and score derived from electroglottographic variables extracted from a previous study. The derived discriminant function's statistical significance was determined via Wilk's λ test (and the associated p value)...
February 15, 2018: Neurological Sciences
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