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Multiple sclerosis biomarkers

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https://www.readbyqxmd.com/read/28229303/phospholipase-d1-expression-analysis-in-relapsing-remitting-multiple-sclerosis-patients
#1
Mohammad Mahdi Eftekharian, Tahereh Azimi, Soudeh Ghafouri-Fard, Arezou Sayad, Mir Davood Omrani, Shaghayegh Sarrafzadeh, Roghayeh Abbasalipourkabir, Mehrdokht Mazdeh, Mohammad Taheri
Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including β-interferons (IFNβ) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid...
February 22, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28203530/longitudinal-evaluation-of-cerebral-and-spinal-cord-damage-in-amyotrophic-lateral-sclerosis
#2
Milena de Albuquerque, Lucas Melo T Branco, Thiago Junqueira R Rezende, Helen Maia Tavares de Andrade, Anamarli Nucci, Marcondes Cavalcante França
OBJECTIVE: To evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression. METHODS: Twenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software)...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28197176/multiple-sclerosis-integration-of-modeling-with-biology-clinical-and-imaging-measures-to-provide-better-monitoring-of-disease-progression-and-prediction-of-outcome
#3
REVIEW
Shikha Jain Goodwin
Multiple Sclerosis (MS) is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a variety of locations throughout the brain; therefore, this disease is never the same in two patients making it very hard to predict disease progression. A modeling approach which combines clinical, biological and imaging measures to help treat and fight this disorder is needed. In this paper, I will outline MS as a very heterogeneous disorder, review some potential solutions from the literature, demonstrate the need for a biomarker and will discuss how computational modeling combined with biological, clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28188915/machine-learning-based-compartment-models-with-permeability-for-white-matter-microstructure-imaging
#4
Gemma L Nedjati-Gilani, Torben Schneider, Matt G Hall, Niamh Cawley, Ioana Hill, Olga Ciccarelli, Ivana Drobnjak, Claudia A M Gandini Wheeler-Kingshott, Daniel C Alexander
Some microstructure parameters, such as permeability, remain elusive because mathematical models that express their relationship to the MR signal accurately are intractable. Here, we propose to use computational models learned from simulations to estimate these parameters. We demonstrate the approach in an example which estimates water residence time in brain white matter. The residence time τi of water inside axons is a potentially important biomarker for white matter pathologies of the human central nervous system, as myelin damage is hypothesised to affect axonal permeability, and thus τi...
February 8, 2017: NeuroImage
https://www.readbyqxmd.com/read/28188869/decreased-expression-of-sema3a-an-immune-modulator-in-blood-sample-of-multiple-sclerosis-patients
#5
Mahsa Rezaeepoor, Shima Shapoori, Mazdak Ganjalikhani-Hakemi, Masoud Etemadifar, Fereshteh Alsahebfosoul, Nahid Eskandari, Marjan Mansuorian
Semaphorin 3A (Sema3a) as an immune modulator could participate in the pathogenesis of autoimmune diseases. In the current study, we aimed to investigate Sema3A expression in peripheral blood mononuclear cells (PBMCs) and its serum level in relapsing-remitting multiple sclerosis (RRMS) patients. Fifteen newly determined and untreated RRMS patients were chosen and assessed in relapsing and remitting phases in compare with fifteen healthy individuals. In consistent with previous findings in other autoimmune diseases, our results revealed that serum level of Sema3A and its expression in PBMCs of RRMS patients were significantly lower than in normal subjects...
February 7, 2017: Gene
https://www.readbyqxmd.com/read/28188715/-multiple-sclerosis-current-immunological-aspects
#6
Carlos Cuevas-García
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28185158/outcome-measures-in-clinical-trials-for-multiple-sclerosis
#7
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...
February 9, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28180139/metabolomic-signatures-associated-with-disease-severity-in-multiple-sclerosis
#8
Pablo Villoslada, Cristina Alonso, Ion Agirrezabal, Ekaterina Kotelnikova, Irati Zubizarreta, Irene Pulido-Valdeolivas, Albert Saiz, Manuel Comabella, Xavier Montalban, Luisa Villar, Jose Carlos Alvarez-Cermeño, Oscar Fernández, Roberto Alvarez-Lafuente, Rafael Arroyo, Azucena Castro
OBJECTIVE: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. METHODS: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS)...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28174096/retinal-biomarkers-provide-insight-into-cortical-pharmacology-and-disease
#9
REVIEW
Christine To Nguyen, Flora Hui, Jason Charng, Shajan Velaedan, Anna van Koeverden, Jeremiah Kh Lim, Zheng He, Vickie Hy Wong, Algis J Vingrys, Bang V Bui, Magnus Ivarsson
The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself favourable to being a biomarker of the brain. More specifically, the presence of neuronal, vascular and blood-neural barrier parallels in the eye and brain coupled with fast and inexpensive methods to quantify retinal changes make ocular biomarkers an attractive option. This includes its utility as a biomarker for multiple cerebrovascular diseases as well as a drug pharmacology and safety biomarker for the CNS...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28168214/cerebrospinal-fluid-protein-carbonylation-identifies-oxidative-damage-in-autoimmune-demyelination
#10
David N Irani
Oxidative damage occurs in multiple sclerosis, but is difficult to identify antemortem and remains an unknown contributor to disease progression. Carbonylation is a quantitative measure of protein oxidation. Cerebrospinal fluid samples from multiple sclerosis patients showed elevated carbonylated protein levels compared to controls. In experimental autoimmune encephalomyelitis, carbonylated protein levels in cerebrospinal fluid correlated tightly with those found in inflamed spinal cord tissues. Furthermore, concentrations in cerebrospinal fluid and spinal cord responded in parallel to an antioxidant intervention that also attenuated disease symptoms...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28161558/neutrophil-perversion-in-demyelinating-autoimmune-diseases-mechanisms-to-medicine
#11
REVIEW
Courtney S Casserly, Julia C Nantes, Ryder F Whittaker Hawkins, Luc Vallières
Neutrophils are essential to a healthy life, yet pose a threat if improperly controlled. Neutrophil perversion is well documented in a variety of inflammatory disorders (e.g. arthritis, lupus, psoriasis), but is only beginning to be demystified in autoimmune demyelination, the most common cause of neurological disability in young adults. Using the animal model experimental autoimmune encephalomyelitis (EAE), several molecules that help neutrophils invade the central nervous system (CNS) have been identified...
February 2, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28155867/kynurenine-pathway-metabolomics-predicts-and-provides-mechanistic-insight-into-multiple-sclerosis-progression
#12
Chai K Lim, Ayse Bilgin, David B Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V Taylor, Alban Bessede, Bruce J Brew, Gilles J Guillemin
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152396/insulin-resistance-atherogenicity-and-iron-metabolism-in-multiple-sclerosis-with-and-without-depression-associations-with-inflammatory-and-oxidative-stress-biomarkers-and-uric-acid
#13
Sayonara Rangel Oliveira, Ana Paula Kallaur, Josiane Lopes, Andrea Name Colado Simão, Edna Maria Vissoci Reiche, Elaine Regina Delicato de Almeida, Helena Kaminami Morimoto, Wildea Lice de Carvalho Jennings de Pereira, Daniela Frizon Alfieri, Tamires Flauzino, Caio de Meleck Proença, Anna Maria Gomes, Damacio Ramón Kaimen-Maciel, Michael Maes
Depression is accompanied by metabolic disorders in iron metabolism, lipoproteins, and insulin resistance. We measured plasma levels of ferritin, iron, lipids, insulin, and glucose and computed the homeostasis model assessment (HOMA2IR) and atherogenic index of plasma (AIP) in MS patients with and without depression and healthy controls. Explanatory variables were serum uric acid, interleukin (IL)-6, lipid hydroperoxides (CL-LOOH), albumin, and C-reactive protein (CRP). Depression was assessed using the Hospital Anxiety and Depression Scale (HADS), neurological disability using the Expanded Disability Status Scale (EDSS), and disease progression using ∆EDSS over five years earlier...
December 27, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#14
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 1, 2017: Neurology
https://www.readbyqxmd.com/read/28135360/retinal-architecture-and-melanopsin-mediated-pupillary-response-characteristics-a-putative-pathophysiologic-signature-for-the-retino-hypothalamic-tract-in-multiple-sclerosis
#15
Ethan Meltzer, Peter V Sguigna, Adnan Subei, Shin Beh, Eric Kildebeck, Darrel Conger, Amy Conger, Marlen Lucero, Benjamin S Frohman, Ashley N Frohman, Shiv Saidha, Steven Galetta, Peter A Calabresi, Robert Rennaker, Teresa C Frohman, Randy H Kardon, Laura J Balcer, Elliot M Frohman
Importance: A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. Objective: To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response...
January 30, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28120152/copy-number-variations-in-amyotrophic-lateral-sclerosis-piecing-the-mosaic-tiles-together-through-a-systems-biology-approach
#16
REVIEW
Giovanna Morello, Maria Guarnaccia, Antonio Gianmaria Spampinato, Valentina La Cognata, Velia D'Agata, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a devastating and still untreatable motor neuron disease. Despite the molecular mechanisms underlying ALS pathogenesis that are still far from being understood, several studies have suggested the importance of a genetic contribution in both familial and sporadic forms of the disease. In addition to single-nucleotide polymorphisms (SNPs), which account for only a limited number of ALS cases, a consistent number of common and rare copy number variations (CNVs) have been associated to ALS...
January 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28114651/are-mirnas-appropriate-biomarkers-for-radiologic-measures-of-tissue-injury-in-multiple-sclerosis
#17
Darin T Okuda
No abstract text is available yet for this article.
January 23, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28114622/association-between-serum-micrornas-and-magnetic-resonance-imaging-measures-of-multiple-sclerosis-severity
#18
Keren Regev, Brian C Healy, Fariha Khalid, Anu Paul, Renxin Chu, Shahamat Tauhid, Subhash Tummala, Camilo Diaz-Cruz, Radhika Raheja, Maria A Mazzola, Felipe von Glehn, Pia Kivisakk, Sheena L Dupuy, Gloria Kim, Tanuja Chitnis, Howard L Weiner, Roopali Gandhi, Rohit Bakshi
Importance: MicroRNAs (miRNAs) are promising multiple sclerosis (MS) biomarkers. Establishing the association between miRNAs and magnetic resonance imaging (MRI) measures of disease severity will help define their significance and potential impact. Objective: To correlate circulating miRNAs in the serum of patients with MS to brain and spinal MRI. Design, Setting, and Participants: A cross-sectional study comparing serum miRNA samples with MRI metrics was conducted at a tertiary MS referral center...
January 23, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28109694/sirt1-as-a-potential-biomarker-of-response-to-treatment-with-glatiramer-acetate-in-multiple-sclerosis
#19
Daniel Hewes, Alexandru Tatomir, Adam M Kruszewski, Gautam Rao, Cosmin A Tegla, Jonathan Ciriello, Vingh Nguyen, Walter Royal, Christopher Bever, Violeta Rus, Horea Rus
SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses...
January 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28108364/from-natalizumab-to-fingolimod-in-eight-weeks-immunological-clinical-and-radiological-data-in-quest-of-the-optimal-switch
#20
Andrea Harrer, Georg Pilz, Katrin Oppermann, Marlene Sageder, Shahrzad Afazel, Elisabeth Haschke-Becher, Theo Rispens, Annick de Vries, Mark McCoy, Vlado Stevanovic, Wolfgang Hitzl, Eugen Trinka, Jörg Kraus, Johann Sellner, Peter Wipfler
Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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