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SPECIAL FOCUS: 10-year anniversary issue - Review

Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

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References

  • Steinman L. Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 1996;85(3):299-302
  • Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005;23:683-747
  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000;343(13):938-52
  • Weiner HL. The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease? Ann Neurol 2009;65(3):239-48
  • Hafler DA. Multiple sclerosis. J Clin Invest 2004;113(6):788-94
  • Damal K, Stoker E, Foley JF. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action. Biologics 2013;7:247-58
  • Poonawalla AH, Datta S, Juneja V, et al. Composite MRI scores improve correlation with EDSS in multiple sclerosis. Mult Scler 2010;16(9):1117-25
  • Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33(11):1444-52
  • Lourenco P, Shirani A, Saeedi J, et al. Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression. Mult Scler 2012
  • Bakshi R, Thompson AJ, Rocca MA, et al. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol 2008;7(7):615-25
  • Tourdias T, Dousset V. Neuroinflammatory Imaging Biomarkers: Relevance to Multiple Sclerosis and its Therapy. Neurotherapeutics 2012
  • Filippi M, Agosta F. Imaging biomarkers in multiple sclerosis. J Magn Reson Imaging 2010;31(4):770-88
  • Neema M, Stankiewicz J, Arora A, et al.I in multiple sclerosis: what’s inside the toolbox? Neurotherapeutics 2007;4(4):602-17
  • Sargento-Freitas J, Batista S, Macario C, et al. Clinical predictors of an optimal response to natalizumab in multiple sclerosis. J Clin Neurosci 2013;20(5):659-62
  • Rio J, Comabella M, Montalban X. Predicting responders to therapies for multiple sclerosis. Nat Rev Neurol 2009;5(10):553-60
  • Sormani MP, De Stefano N. Defining and scoring response to IFN-beta in multiple sclerosis. Nature reviews. Neurology 2013;9(9):504-12
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69(2):292-302
  • Freedman MS. Long-term follow-up of clinical trials of multiple sclerosis therapies. Neurology 2011;76(1 Suppl 1):S26-34
  • Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13(3):227-31
  • Biomarkers Definitions Working G. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95
  • Katz R. Biomarkers and surrogate markers: an FDA perspective. Neuro 2004;1(2):189-95
  • Ziemann U, Wahl M, Hattingen E, Tumani H. Development of biomarkers for multiple sclerosis as a neurodegenerative disorder. Prog Neurobiol 2011;95(4):670-85
  • Gomes Mda M, Engelhardt E. Jean-Martin Charcot, father of modern neurology: an homage 120 years after his death. Arq Neuropsiquiatr 2013;71(10):815-17
  • Carswell R. Pathological anatomy. Illustrations of the elementary forms of disease (Longman, Orme, Brown, Green and Longman, London; 1838
  • Compston A. The 150th anniversary of the first depiction of the lesions of multiple sclerosis. J Neurol Neurosurg Psychiatry 1988;51(10):1249-52
  • Talley CL. A history of multiple sclerosis. Praeger; Westport: Conn: 2008
  • Tsafrir I, Guedeau-Boudeville MA, Kandel D, Stavans J. Coiling instability of multilamellar membrane tubes with anchored polymers. Phys Rev E Stat Nonlin Soft Matter Phys 2001;63(3 Pt 1):031603
  • Rivers TM, Sprunt DH, Berry GP. Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 1933;58(1):39-53
  • Schwentker FF, Rivers TM. The antibody response of rabbits to injections of emulsions and extracts of homologous brain. J Exp Med 1934;60(5):559-74
  • Rivers TM, Schwentker FF. Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J Exp Med 1935;61(5):689-702
  • Hurst EW. The effects of the injection of normal brain emulsion into rabbits, with special reference to the aetiology of the paralytic accidents of antirabic treatment. J Hyg (Lond) 1932;32(1):33-44
  • Morgan IM. Allergic encephalomyelitis in monkeys in response to injection of normal monkey nervous tissue. J Exp Med 1947;85(1):131-40
  • Kabat EA, Wolf A, Bezer AE. The rapid production of acute disseminated encephalomyelitis in Rhesus monkeys by injection of heterologous and homologous brain tissue with adjuvants. J Exp Med 1947;85(1):117-30
  • Robinson AP, Harp CT, Noronha A, Miller SD. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment. Handb Clin Neurol 2014;122:173-89
  • Steinman L. Optic neuritis, a new variant of experimental encephalomyelitis, a durable model for all seasons, now in its seventieth year. J Exp Med 2003;197(9):1065-71
  • Kabat EA, Moore DH, Landow H. An electrophoretic study of the protein components in cerebrospinal fluid and their relationship to the serum proteins. J Clin Invest 1942;21(5):571-7
  • Green F. The colloidal gold reaction of the cerebrospinal fluid. Can Med Assoc J 1925;15(11):1139-43
  • McDiarmid N. The value of routine examination of the cerebrospinal fluid: report on the examination of 3,200 fluids. J Neurol Psychopathol 1931;11(43):247-54
  • Kabat EA, Glusman M, Knaub V. Quantitative estimation of the albumin and gamma globulin in normal and pathologic cerebrospinal fluid by immunochemical methods. Am J Med 1948;4(5):653-62
  • Lowenthal A, Vansande M, Karcher D. The differential diagnosis of neurological diseases by fractionating electrophoretically the CSF gamma-globulins. J Neurochem 1960;6:51-6
  • Davenport RD, Keren DF. Oligoclonal bands in cerebrospinal fluids: significance of corresponding bands in serum for diagnosis of multiple sclerosis. Clin Chem 1988;34(4):764-5
  • Young IR, Hall AS, Pallis CA, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981;2(8255):1063-6
  • Gajofatto A, Calabrese M, Benedetti MD, Monaco S. Clinical, MRI, and CSF markers of disability progression in multiple sclerosis. Dis Markers 2013;35(6):687-99
  • Olek MJ. Multiple sclerosis: etiology, diagnosis, and new treatment strategies. Humana Press; Totowa, N.J: 2005
  • Schumacker GA, Beebe G, Kibler RF, et al. Problems of experimental trials of therapy in multiple sclerosis: report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis. Ann N Y Acad Sci 1965;122:552-68
  • Miller DH, Weinshenker BG, Filippi M, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008;14(9):1157-74
  • McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50(1):121-7
  • Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria’. Ann Neurol 2005;58(6):840-6
  • Milo R, Miller A. Revised diagnostic criteria of multiple sclerosis. Autoimmun Rev 2014;13(4-5):518-24
  • Stangel M, Fredrikson S, Meinl E, et al. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol 2013;9(5):267-76
  • Tumani H, Deisenhammer F, Giovannoni G, et al. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol 2011;70(3):520; author reply 521
  • Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014;83(3):278-86
  • Cross AH, Wingerchuk DM, Weinshenker BG. Active and progressive: a new duality of MS classification. Neurology 2014;83(3):206-7
  • Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007;8(2):93-103
  • O’Connell RM, Rao DS, Baltimore D. MicroRNA regulation of inflammatory responses. Annu Rev Immunol 2012;30:295-312
  • Baumjohann D, Ansel KM. MicroRNA-mediated regulation of T helper cell differentiation and plasticity. Nat Reviews Immunol 2013;13(9):666-78
  • Liu NK, Xu XM. MicroRNA in central nervous system trauma and degenerative disorders. Physiol Genomics 2011;43(10):571-80
  • Moreno-Moya JM, Vilella F, Simon C. MicroRNA: key gene expression regulators. Fertil Steril 2014;101(6):1516-23
  • Rao P, Benito E, Fischer A. MicroRNAs as biomarkers for CNS disease. Front Mol Neurosci 2013;6:39
  • Otaegui D, Baranzini SE, Armananzas R, et al. Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One 2009;4(7):e6309
  • Lindberg RL, Hoffmann F, Mehling M, et al. Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol 2010;40(3):888-98
  • Keller A, Leidinger P, Lange J, et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One 2009;4(10):e7440
  • Siegel SR, Mackenzie J, Chaplin G, et al. Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 2012;39(5):6219-25
  • Fenoglio C, Ridolfi E, Cantoni C, et al. Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis. Mult Scler 2013;19(14):1938-42
  • Ridolfi E, Fenoglio C, Cantoni C, et al. Expression and genetic analysis of microRNAs involved in multiple sclerosis. Int J Mol Sci 2013;14(3):4375-84
  • Du C, Liu C, Kang J, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 2009;10(12):1252-9
  • Junker A, Krumbholz M, Eisele S, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009;132(Pt 12):3342-52
  • Cox MB, Cairns MJ, Gandhi KS, et al. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 2010;5(8):e12132
  • Sievers C, Meira M, Hoffmann F, et al. Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. Clinical immunology 2012;144(1):70-9
  • Haghikia A, Haghikia A, Hellwig K, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology 2012;79(22):2166-70
  • Guerau-de-Arellano M, Smith KM, Godlewski J, et al. Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain 2011;134(Pt 12):3578
  • Thamilarasan M, Koczan D, Hecker M, et al. MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun Rev 2012;11(3):174-9
  • O’Connell RM, Taganov KD, Boldin MP, et al. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007. 104(5):1604-9
  • Wu X, Fan W, Fang R, Wu G. Regulation of microRNA-155 in endothelial inflammation by targeting nuclear factor (NF)-kappaB P65. J Cell Biochem 2014;115(11):1928-36
  • Chen F, Hu SJ. Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol 2012;26(2):79-86
  • Schmidt H, Williamson D, Ashley-Koch A. HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol 2007;165(10):1097-109
  • Kim RY, Xu H, Myllykangas S, Ji H. Genetic-based biomarkers and next-generation sequencing: the future of personalized care in colorectal cancer. Personalized medicine 2011;8(3):331-45
  • Comabella M, Martin R. Genomics in multiple sclerosis-current state and future directions. J Neuroimmunol 2007;187(1-2):1-8
  • Achiron A, Gurevich M. Peripheral blood gene expression signature mirrors central nervous system disease: the model of multiple sclerosis. Autoimmun Rev 2006;5(8):517-22
  • Bomprezzi R, Ringner M, Kim S, et al. Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease. Hum Mol Genet 2003;12(17):2191-9
  • Zuvich RL, McCauley JL, Oksenberg JR, et al. Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility. Hum Genet 2010;127(5):525-35
  • Achiron A, Feldman A, Mandel M, Gurevich M. Impaired expression of peripheral blood apoptotic-related gene transcripts in acute multiple sclerosis relapse. Ann N Y Acad Sci 2007;1107:155-67
  • Brynedal B, Khademi M, Wallstrom E, et al. Gene expression profiling in multiple sclerosis: a disease of the central nervous system, but with relapses triggered in the periphery? Neurobiol Dis 2010;37(3):613-21
  • Booth DR, Arthur AT, Teutsch SM, et al. Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis. J Mol Med 2005;83(10):822-30
  • Hecker M, Paap BK, Goertsches RH, et al. Reassessment of blood gene expression markers for the prognosis of relapsing-remitting multiple sclerosis. PLoS One 2011;6(12):e29648
  • Satoh J, Nakanishi M, Koike F, et al. Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis. Neurobiol Dis 2005;18(3):537-50
  • Romme-Christensen J, Bornsen L, Hesse D, et al. Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis. J Neuroinflammation 2012;9:215
  • Hecker M, Goertsches RH, Fatum C, et al. Network analysis of transcriptional regulation in response to intramuscular interferon-beta-1a multiple sclerosis treatment. Pharmacogenomics J 2012;12(4):360
  • Hecker M, Goertsches RH, Fatum C, et al. Network analysis of transcriptional regulation in response to intramuscular interferon-beta-1a multiple sclerosis treatment. Pharmacogenomics J 2012;12(2):134-46
  • Goertsches RH, Hecker M, Koczan D, et al. Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS. Pharmacogenomics 2010;11(2):147-61
  • Serrano-Fernandez P, Moller S, Goertsches R, et al. Time course transcriptomics of IFNB1b drug therapy in multiple sclerosis. Autoimmunity 2010;43(2):172-8
  • Singh MK, Scott TF, LaFramboise WA, et al. Gene expression changes in peripheral blood mononuclear cells from multiple sclerosis patients undergoing beta-interferon therapy. J Neurol Sci 2007;258(1-2):52-9
  • Sturzebecher S, Wandinger KP, Rosenwald A, et al. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain 2003;126(Pt 6):1419-29
  • Weinstock-Guttman B, Badgett D, Patrick K, et al. Genomic effects of IFN-beta in multiple sclerosis patients. J Immunol 2003;171(5):2694-702
  • Hong J, Zang YC, Hutton G, et al. Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. J Neuroimmunol 2004;152(1-2):126-39
  • Achiron A, Feldman A, Gurevich M. Molecular profiling of glatiramer acetate early treatment effects in multiple sclerosis. Dis Markers 2009;27(2):63-73
  • Khademi M, Bornsen L, Rafatnia F, et al. The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers. Eur J Neurol 2009;16(4):528-36
  • von Wussow P, Jakschies D, Hochkeppel HK, et al. The human intracellular Mx-homologous protein is specifically induced by type I interferons. Eur J Immunol 1990;20(9):2015-19
  • Killestein J, Polman CH. Determinants of interferon beta efficacy in patients with multiple sclerosis. Nature reviews. Neurology 2011;7(4):221-8
  • Bertolotto A, Gilli F, Sala A, et al. Evaluation of bioavailability of three types of IFNbeta in multiple sclerosis patients by a new quantitative-competitive-PCR method for MxA quantification. J Immunol Methods 2001;256(1-2):141-52
  • Pachner AR, Bertolotto A, Deisenhammer F. Measurement of MxA mRNA or protein as a biomarker of IFNbeta bioactivity: detection of antibody-mediated decreased bioactivity (ADB). Neurology 2003;61(9 Suppl 5):S24-6
  • Malucchi S, Gilli F, Caldano M, et al. Predictive markers for response to interferon therapy in patients with multiple sclerosis. Neurology 2008;70(13 Pt 2):1119-1127
  • Lindberg RL, Kappos L. Transcriptional profiling of multiple sclerosis: towards improved diagnosis and treatment. Expert Rev Mol Diagn 2006;6(6):843-55
  • Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002;1(11):845-67
  • Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 2006;24(8):971-83
  • Tian Y, Apperson ML, Ander BP, et al. Differences in exon expression and alternatively spliced genes in blood of multiple sclerosis compared to healthy control subjects. J Neuroimmunol 2011;230(1-2):124-9
  • Sanchez-Pla A, Reverter F, Ruiz de Villa MC, Comabella M. Transcriptomics: mRNA and alternative splicing. J Neuroimmunol 2012;248(1-2):23-31
  • Adibhatla RM, Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem 2008;49:241-68
  • Giubilei F, Antonini G, Di Legge S, et al. Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis. Acta Neurol Scand 2002;106(2):109-12
  • Bretillon L, Siden A, Wahlund LO, et al. Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci Lett 2000;293(2):87-90
  • Quintana FJ, Yeste A, Weiner HL, Covacu R. Lipids and lipid-reactive antibodies as biomarkers for multiple sclerosis. J Neuroimmunol 2012;248(1-2):53-7
  • Leoni V. Oxysterols as markers of neurological disease-a review. Scand J Clin Lab Invest 2009;69(1):22-5
  • Dietschy JM, Turley SD. Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 2004;45(8):1375-97
  • Leoni V, Caccia C. Oxysterols as biomarkers in neurodegenerative diseases. Chem Phys Lipids 2011;164(6):515-24
  • Ramsey RB, Nicholas HJ. Unusual urinary cholesterol metabolites following intracerebral injection of [4-14C]cholesterol into rats: I. The minor 14C-metabolite. Lipids 1982;17(3):263-7
  • Nicholas HJ, Taylor J. Central nervous system demyelinating diseases and increased release of cholesterol into the urinary system of rats. Lipids 1994;29(9):611-17
  • Shore VG, Smith ME, Perret V, Laskaris MA. Alterations in plasma lipoproteins and apolipoproteins in experimental allergic encephalomyelitis. J Lipid Res 1987;28(2):119-29
  • Weinstock-Guttman B, Zivadinov R, Mahfooz N, et al. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation 2011;8:127
  • Subedi BH, Joshi PH, Jones SR, et al. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions. Vasc Health Risk Manag 2014;10:205-16
  • Ciurleo R, Bramanti P, Marino S. Role of statins in the treatment of multiple sclerosis. Pharmacol Res 2014;87:133-43
  • Leoni V, Masterman T, Diczfalusy U, et al. Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci Lett 2002;331(3):163-6
  • Karrenbauer VD, Leoni V, Lim ET, et al. Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis. Clin Neurol Neurosurg 2006;108(5):456-60
  • Teunissen CE, Dijkstra CD, Polman CH, et al. Decreased levels of the brain specific 24S-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci Lett 2003;347(3):159-62
  • Teunissen CE, Floris S, Sonke M, et al. 24S-hydroxycholesterol in relation to disease manifestations of acute experimental autoimmune encephalomyelitis. J Neurosci Res 2007;85(7):1499-505
  • Leoni V, Caccia C. Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid. Biochem Pharmacol 2013;86(1):26-36
  • Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain pathology 1999;9(1):69-92
  • Chang JY, Liu LZ. Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells. Neurochem Int 1998;32(4):317-23
  • Chang JY, Phelan KD, Chavis JA. Neurotoxicity of 25-OH-cholesterol on sympathetic neurons. Brain Res Bull 1998;45(6):615-22
  • Chang JY, Phelan KD, Liu LZ. Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells. Neurochem Res 1998;23(1):7-16
  • Diestel A, Aktas O, Hackel D, et al. Activation of microglial poly(ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J Exp Med 2003;198(11):1729-40
  • Leoni V, Lutjohann D, Masterman T. Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis. J Lipid Res 2005;46(2):191-5
  • Farez MF, Quintana FJ, Gandhi R, et al. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat Immunol 2009;10(9):958-64
  • Haider L, Fischer MT, Frischer JM, et al. Oxidative damage in multiple sclerosis lesions. Brain 2011;134(Pt 7):1914-24
  • Sbardella E, Greco A, Stromillo ML, et al. Isoprostanes in clinically isolated syndrome and early multiple sclerosis as biomarkers of tissue damage and predictors of clinical course. Mult Scler 2013;19(4):411-17
  • Teunissen CE, Sombekke M, van Winsen L, et al. Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression. Mult Scler 2012;18(8):1092-8
  • Miller E, Mrowicka M, Saluk-Juszczak J, Ireneusz M. The level of isoprostanes as a non-invasive marker for in vivo lipid peroxidation in secondary progressive multiple sclerosis. Neurochem Res 2011;36(6):1012-16
  • Koch M, Mostert J, Arutjunyan AV, et al. Plasma lipid peroxidation and progression of disability in multiple sclerosis. Eur J Neurol 2007;14(5):529-33
  • Greco A, Minghetti L, Puopolo M, et al. Cerebrospinal fluid isoprostanes are not related to inflammatory activity in relapsing-remitting multiple sclerosis. J Neurol Sci 2004;224(1-2):23-7
  • Naidoo R, Knapp ML. Studies of lipid peroxidation products in cerebrospinal fluid and serum in multiple sclerosis and other conditions. Clin Chem 1992;38(12):2449-54
  • Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005;5(11):845-56
  • Howes JM, Keen JN, Findlay JB, Carter AM. The application of proteomics technology to thrombosis research: the identification of potential therapeutic targets in cardiovascular disease. Diab Vasc Dis Res 2008;5(3):205-12
  • van Venrooij WJ, Vossenaar ER, Zendman AJ. Anti-CCP antibodies: the new rheumatoid factor in the serology of rheumatoid arthritis. Autoimmun Rev 2004(3 Suppl 1):S17-19
  • von Muhlen CA, Tan EM. Autoantibodies in the diagnosis of systemic rheumatic diseases. Semin Arthritis Rheum 1995;24(5):323-58
  • Berger JR, Dean D. Neurosyphilis. Handb Clin Neurol 2014;121:1461-72
  • Kherad O, Kaiser L, Bridevaux PO, et al. Upper-respiratory viral infection, biomarkers, and COPD exacerbations. Chest 2010;138(4):896-904
  • Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR. Recomm Rep 2001;50(RR-19):1-57. quiz CE51-19a51-CE56-19a51
  • Jaros JA, Guest PC, Bahn S, Martins-de-Souza D. Affinity depletion of plasma and serum for mass spectrometry-based proteome analysis. Methods Mol Biol 2013;1002:1-11
  • Rodriguez-Rodriguez A, Egea-Guerrero JJ, Leon-Justel A, et al. Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults. Clin Chim Acta 2012;414:228-33
  • Muraro PA, Leist T, Bielekova B, McFarland HF. VLA-4/CD49d downregulated on primed T lymphocytes during interferon-beta therapy in multiple sclerosis. J Neuroimmunol 2000;111(1-2):186-94
  • Schiott A, Lindstedt M, Johansson-Lindbom B, et al.27- CD4+ memory T cells define a differentiated memory population at both the functional and transcriptional levels. Immunology 2004;113(3):363-70
  • Zafranskaya M, Oschmann P, Engel R, et al. Interferon-beta therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis. Immunology 2007;121(1):29-39
  • Chatzimanolis N, Kraus J, Bauer R, et al. CD45RA+ ICAM-3+ lymphocytes in interferon-beta1b-treated and -untreated patients with relapsing-remitting multiple sclerosis. Acta Neurol Scand 2004;110(6):377-85
  • Wang HY, Matsui M, Araya S, et al. Immune parameters associated with early treatment effects of high-dose intravenous methylprednisolone in multiple sclerosis. J Neurol Sci 2003;216(1):61-6
  • Franciotta DM, Grimaldi LM, Martino GV, et al. Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis. Ann Neurol 1989;26(6):787-9
  • Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325(7):467-72
  • Drulovic J, Mostarica-Stojkovic M, Levic Z, et al. Interleukin-12 and tumor necrosis factor-alpha levels in cerebrospinal fluid of multiple sclerosis patients. J Neurol Sci 1997;147(2):145-50
  • Vladic A, Horvat G, Vukadin S, et al. Cerebrospinal fluid and serum protein levels of tumour necrosis factor-alpha (TNF-alpha) interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R gp80) in multiple sclerosis patients. Cytokine 2002;20(2):86-9
  • Stelmasiak Z, Koziol-Montewka M, Dobosz B, et al. Interleukin-6 concentration in serum and cerebrospinal fluid in multiple sclerosis patients. Med Sci Monit 2000;6(6):1104-8
  • Malmestrom C, Andersson BA, Haghighi S, Lycke J. IL-6 and CCL2 levels in CSF are associated with the clinical course of MS: implications for their possible immunopathogenic roles. J Neuroimmunol 2006;175(1-2):176-82
  • Chen YC, Yang X, Miao L, et al. Serum level of interleukin-6 in Chinese patients with multiple sclerosis. J Neuroimmunol 2012;249(1-2):109-11
  • Zepp J, Wu L, Li X. IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol 2011;32(5):232-9
  • Axtell RC, de Jong BA, Boniface K, et al. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med 2010;16(4):406-12
  • Lee LF, Axtell R, Tu GH, et al. IL-7 promotes T(H)1 development and serum IL-7 predicts clinical response to interferon-beta in multiple sclerosis. Sci Transl Med 2011;3(93):93ra68
  • Balasa R, Bajko Z, Hutanu A. Serum levels of IL-17A in patients with relapsing-remitting multiple sclerosis treated with interferon-beta. Mult Scler 2013;19(7):885-90
  • Hartung HP, Steinman L, Goodin DS, et al. Interleukin 17F level and interferon beta response in patients with multiple sclerosis. JAMA Neurol 2013;70(8):1017-21
  • Maimone D, Gregory S, Arnason BG, Reder AT. Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J Neuroimmunol 1991;32(1):67-74
  • Rentzos M, Cambouri C, Rombos A, et al. IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci 2006;241(1-2):25-9
  • Nguyen LT, Ramanathan M, Weinstock-Guttman B, et al. Sex differences in in vitro pro-inflammatory cytokine production from peripheral blood of multiple sclerosis patients. J Neurol Sci 2003;209(1-2):93-9
  • Nicoletti F, Patti F, Cocuzza C, et al. Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis. J Neuroimmunol 1996;70(1):87-90
  • Chen YC, Chen SD, Miao L, et al. Serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with multiple sclerosis. J Neuroimmunol 2012;243(1-2):56-60
  • Krumbholz M, Theil D, Cepok S, et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 2006;129(Pt 1):200-11
  • Bielekova B, Komori M, Xu Q, et al. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation. PLoS One 2012;7(11):e48370
  • Alvarez E, Piccio L, Mikesell RJ, et al. CXCL13 is a biomarker of inflammation in multiple sclerosis, neuromyelitis optica, and other neurological conditions. Mult Scler 2013;19(9):1204-8
  • Romme-Christensen J, Bornsen L, Khademi M, et al. CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis. Mult Scler 2013;19(7):877-84
  • Festa ED, Hankiewicz K, Kim S, et al. Serum levels of CXCL13 are elevated in active multiple sclerosis. Mult Scler 2009;15(11):1271-9
  • Ljostad U, Mygland A. CSF B-lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis. J Neurol 2008;255(5):732-7
  • Rupprecht TA, Pfister HW, Angele B, et al. The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis. Neurology 2005;65(3):448-50
  • O’Connell KE, Mok T, Sweeney B, et al. The use of cytokine signature patterns: separating drug naive, interferon and natalizumab-treated multiple sclerosis patients. Autoimmunity 2014;47(8):505-11
  • Hagman S, Raunio M, Rossi M, et al. Disease-associated inflammatory biomarker profiles in blood in different subtypes of multiple sclerosis: prospective clinical and MRI follow-up study. J Neuroimmunol 2011;234(1-2):141-7
  • Tomizawa Y, Yokoyama K, Saiki S, et al. Blood-brain barrier disruption is more severe in neuromyelitis optica than in multiple sclerosis and correlates with clinical disability. J Int Med Res 2012;40(4):1483-91
  • Avolio C, Ruggieri M, Giuliani F, et al. Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes. J Neuroimmunol 2003;136(1-2):46-53
  • Sellebjerg F, Sorensen TL. Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system. Brain Res Bull 2003;61(3):347-55
  • Fainardi E, Castellazzi M, Bellini T, et al. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 2006;12(3):294-301
  • Waubant E, Goodkin D, Bostrom A, et al. IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS. Neurology 2003;60(1):52-7
  • Avolio C, Filippi M, Tortorella C, et al. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment. Mult Scler 2005;11(4):441-6
  • Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol 2006;180(1-2):17-28
  • Haertle M, Kallweit U, Weller M, Linnebank M. The presence of oligoclonal IgG bands in human CSF during the course of neurological diseases. J Neurol 2014;261(3):554-60
  • Alvarez-Cermeno JC, Villar LM. Multiple sclerosis: oligoclonal bands-a useful tool to avoid MS misdiagnosis. Nature reviews. Neurology 2013;9(6):303-4
  • Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis. J Neurol 2010;257(7):1188-91
  • Correale J, de los Milagros Bassani Molinas M. Oligoclonal bands and antibody responses in multiple sclerosis. J Neurol 2002;249(4):375-89
  • Owens GP, Bennett JL, Lassmann H, et al. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Ann Neurol 2009;65(6):639-49
  • Beltran E, Obermeier B, Moser M, et al. Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation. Brain 2014;137(Pt 10):2703-14
  • Villar L, Garcia-Barragan N, Espino M, et al. Influence of oligoclonal IgM specificity in multiple sclerosis disease course. Mult Scler 2008;14(2):183-7
  • Schneider R, Euler B, Rauer S. Intrathecal IgM-synthesis does not correlate with the risk of relapse in patients with a primary demyelinating event. Eur J Neurol 2007;14(8):907-11
  • Garcia-Barragan N, Villar LM, Espino M, et al. Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment. Eur J Neurol 2009;16(3):380-5
  • Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry 2013;84(8):909-14
  • Nilsson P, Larsson EM, Maly-Sundgren P, et al. Predicting the outcome of optic neuritis: evaluation of risk factors after 30 years of follow-up. J Neurol 2005;252(4):396-402
  • Cross AH, Wu GF. Multiple sclerosis: oligoclonal bands still yield clues about multiple sclerosis. Nat Rev Neurol 2010;6(11):588-9
  • Antel JP, Bar-Or A. Do myelin-directed antibodies predict multiple sclerosis? N Engl J Med 2003;349(2):107-9
  • Berger T, Reindl M. Immunopathogenic and clinical relevance of antibodies against myelin oligodendrocyte glycoprotein (MOG) in Multiple Sclerosis. J Neural Transm Suppl 2000(60):351-60
  • de Seze J, Dubucquoi S, Lefranc D, et al. IgG reactivity against citrullinated myelin basic protein in multiple sclerosis. J Neuroimmunol 2001;117(1-2):149-55
  • Reindl M, Linington C, Brehm U, et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999;122(Pt 11):2047-56
  • Berger T, Rubner P, Schautzer F, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003;349(2):139-45
  • Kuhle J, Pohl C, Mehling M, et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 2007;356(4):371-8
  • Berger T, Reindl M. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 2007;356(18):1888-9. author reply 1888-1889
  • Quintana FJ, Farez MF, Viglietta V, et al. Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis. Proc Natl Acad Sci USA 2008;105(48):18889-94
  • Srivastava R, Aslam M, Kalluri SR, et al. Potassium channel KIR4.1 as an immune target in multiple sclerosis. N Engl J Med 2012;367(2):115-23
  • Nerrant E, Salsac C, Charif M, et al. Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis. Mult Scler 2014;20(13):1699-703
  • Brickshawana A, Hinson SR, Romero MF, et al. Investigation of the KIR4.1 potassium channel as a putative antigen in patients with multiple sclerosis: a comparative study. Lancet Neurol 2014;13(8):795-806
  • Filippi M, Rocca MA, Lassmann H. KIR4.1: another misleading expectation in multiple sclerosis? Lancet Neurol 2014;13(8):753-5
  • Hedegaard CJ, Chen N, Sellebjerg F, et al. Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. Immunology 2009;128(1 Suppl):e451-61
  • Elkarim RA, Mustafa M, Kivisakk P, et al. Cytokine autoantibodies in multiple sclerosis, aseptic meningitis and stroke. Eur J Clin Invest 1998;28(4):295-9
  • Watanabe M, Uchida K, Nakagaki K, et al. High avidity cytokine autoantibodies in health and disease: pathogenesis and mechanisms. Cytokine Growth Factor Rev 2010;21(4):263-73
  • Cameron EM, Spencer S, Lazarini J, et al. Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis. J Neuroimmunol 2009;213(1-2):123-30
  • Ligocki AJ, Lovato L, Xiang D, et al. A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis. J Neuroimmunol 2010;226(1-2):192-3
  • Rosche B, Laurent S, Conradi S, et al. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis. PLoS One 2012;7(1):e28094
  • Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 1998;4(3):111-17
  • Brettschneider J, Tumani H, Kiechle U, et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One 2009;4(11):e7638
  • Simon KC, O’Reilly EJ, Munger KL, et al. Epstein-Barr virus neutralizing antibody levels and risk of multiple sclerosis. Mult Scler 2012;18(8):1185-7
  • Bray PF, Luka J, Bray PF, et al. Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein. Neurology 1992;42(9):1798-804
  • Willis SN, Stadelmann C, Rodig SJ, et al. Epstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 2009;132(Pt 12):3318-28
  • Lunemann JD, Edwards N, Muraro PA, et al. Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 2006;129(Pt 6):1493-506
  • Cepok S, Zhou D, Srivastava R, et al. Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J Clin Invest 2005;115(5):1352-60
  • De Jager PL, Simon KC, Munger KL, et al. Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis. Neurology 2008;70(13 Pt 2):1113-18
  • Skorstad G, Vandvik B, Vartdal F, Holmoy T. MS and clinically isolated syndromes: shared specificity but diverging clonal patterns of virus-specific IgG antibodies produced in vivo and by CSF B cells in vitro. Eur J Neurol 2009;16(10):1124-9
  • Lamdhade S, Ashkanani A, Alroughani R. Prevalence of Anti-JC Virus Antibody in Multiple Sclerosis Patients in Kuwait. ISRN Neurology 2014;2014:861091
  • Marrie RA. When one and one make three: HLA and EBV infection in MS. Neurology 2008;70(13 Pt 2):1067-8
  • Sellebjerg F, Christiansen M, Garred P. MBP, anti-MBP and anti-PLP antibodies, and intrathecal complement activation in multiple sclerosis. Mult Scler 1998;4(3):127-31
  • Whitaker JN. Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis. Neurology 1977;27(10):911-20
  • Whitaker JN, Lisak RP, Bashir RM, et al. Immunoreactive myelin basic protein in the cerebrospinal fluid in neurological disorders. Ann Neurol 1980;7(1):58-64
  • Lamers KJ, de Reus HP, Jongen PJ. Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis. Mult Scler 1998;4(3):124-6
  • Barkhof F, Frequin ST, Hommes OR, et al. A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone. Neurology 1992;42(1):63-7
  • Raphael I, Mahesula S, Kalsaria K, et al. Microwave and magnetic (M(2)) proteomics of the experimental autoimmune encephalomyelitis animal model of multiple sclerosis. Electrophoresis 2012;33(24):3810-19
  • Mahesula S, Raphael I, Raghunathan R, et al. Immunoenrichment microwave and magnetic proteomics for quantifying CD47 in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Electrophoresis 2012;33(24):3820-9
  • Su E, Bell MJ, Kochanek PM, et al. Increased CSF concentrations of myelin basic protein after TBI in infants and children: absence of significant effect of therapeutic hypothermia. Neurocrit Care 2012;17(3):401-7
  • Verbeek MM, De Jong D, Kremer HP. Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases. Ann Clin Biochem 2003;40(Pt 1):25-40
  • Dutta R, Trapp BD. Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 2007;68(22 Suppl 3):S22-31. discussion S43-54
  • Agius MA, Kirvan CA, Schafer AL, et al. High prevalence of anti-alpha-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease. Acta Neurol Scand 1999;100(3):139-47
  • Stoevring B, Vang O, Christiansen M. (alpha)B-crystallin in cerebrospinal fluid of patients with multiple sclerosis. Clin Chim Acta 2005;356(1-2):95-101
  • Vojdani A, Vojdani E, Cooper E. Antibodies to myelin basic protein, myelin oligodendrocytes peptides, alpha-beta-crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis. J Intern Med 2003;254(4):363-74
  • Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol 2011;93(3):421-43
  • Massaro AR, Tonali P. Cerebrospinal fluid markers in multiple sclerosis: an overview. Mult Scler 1998;4(1):1-4
  • Axelsson M, Malmestrom C, Nilsson S, et al. Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis. J Neurol 2011;258(5):882-8
  • Takano R, Misu T, Takahashi T, et al. Astrocytic damage is far more severe than demyelination in NMO: a clinical CSF biomarker study. Neurology 2010;75(3):208-16
  • Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 2005;233(1-2):183-98
  • Bartos A, Fialova L, Soukupova J, et al. Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis. J Neurol 2007;254(1):20-5
  • Krishnamoorthy G, Saxena A, Mars LT, et al. Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis. Nat Med 2009;15(6):626-32
  • Norgren N, Sundstrom P, Svenningsson A, et al. Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology 2004;63(9):1586-90
  • Teunissen CE, Iacobaeus E, Khademi M, et al. Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 2009;72(15):1322-9
  • Kuhle J, Plattner K, Bestwick JP, et al. A comparative study of CSF neurofilament light and heavy chain protein in MS. Mult Scler 2013;19(12):1597-603
  • Gunnarsson M, Malmestrom C, Axelsson M, et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 2011;69(1):83-9
  • Petzold A, Eikelenboom MJ, Keir G, et al. Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study. J Neurol Neurosurg Psychiatry 2005;76(2):206-11
  • Kuhle J, Leppert D, Petzold A, et al. Neurofilament heavy chain in CSF correlates with relapses and disability in multiple sclerosis. Neurology 2011;76(14):1206-13
  • Lim ET, Sellebjerg F, Jensen CV, et al. Acute axonal damage predicts clinical outcome in patients with multiple sclerosis. Mult Scler 2005;11(5):532-6
  • Brettschneider J, Petzold A, Junker A, Tumani H. Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis. Mult Scler 2006;12(2):143-8
  • Petzold A, Mondria T, Kuhle J, et al. Evidence for acute neurotoxicity after chemotherapy. Ann Neurol 2010;68(6):806-15
  • Kuhle J, Malmestrom C, Axelsson M, et al. Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis. Acta Neurol Scand 2013;128(6):e33-6
  • Gajofatto A, Bongianni M, Zanusso G, et al. Are cerebrospinal fluid biomarkers useful in predicting the prognosis of multiple sclerosis patients? Int J Mol Sci 2011;12(11):7960-70
  • Colucci M, Roccatagliata L, Capello E, et al. The 14-3-3 protein in multiple sclerosis: a marker of disease severity. Mult Scler 2004;10(5):477-81
  • Bartosik-Psujek H, Archelos JJ. Tau protein and 14-3-3 are elevated in the cerebrospinal fluid of patients with multiple sclerosis and correlate with intrathecal synthesis of IgG. J Neurol 2004;251(4):414-20
  • Terzi M, Birinci A, Cetinkaya E, Onar MK. Cerebrospinal fluid total tau protein levels in patients with multiple sclerosis. Acta Neurol Scand 2007;115(5):325-30
  • Kapaki E, Paraskevas GP, Michalopoulou M, Kilidireas K. Increased cerebrospinal fluid tau protein in multiple sclerosis. Eur Neurol 2000;43(4):228-32
  • Jaworski J, Psujek M, Janczarek M, et al. Total-tau in cerebrospinal fluid of patients with multiple sclerosis decreases in secondary progressive stage of disease and reflects degree of brain atrophy. Ups J Med Sci 2012;117(3):284-92
  • Jimenez-Jimenez FJ, Zurdo JM, Hernanz A, et al. Tau protein concentrations in cerebrospinal fluid of patients with multiple sclerosis. Acta Neurol Scand 2002;106(6):351-4
  • Fiorini M, Zanusso G, Benedetti MD, et al. Cerebrospinal fluid biomarkers in clinically isolated syndromes and multiple sclerosis. Proteomics Clin Appl 2007;1(9):963-71
  • Holtzman DM. CSF biomarkers for Alzheimer’s disease: current utility and potential future use. Neurobiol Aging 2011;32(Suppl 1):S4-9
  • Stoeck K, Sanchez-Juan P, Gawinecka J, et al. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years. Brain 2012;135(Pt 10):3051-61
  • Kister I, Bacon TE, Chamot E, et al. Natural history of multiple sclerosis symptoms. Int J MS Care 2013;15(3):146-58
  • Runmarker B, Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 1993;116(Pt 1):117-34
  • Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003;126(Pt 4):770-82
  • Farias AS, Pradella F, Schmitt A, et al. Ten years of proteomics in multiple sclerosis. Proteomics 2014;14(4-5):467-80
  • Del Boccio P, Pieragostino D, Di Ioia M, et al. Lipidomic investigations for the characterization of circulating serum lipids in multiple sclerosis. J Proteomics 2011;74(12):2826-36
  • Quintana FJ, Farez MF, Weiner HL. Systems biology approaches for the study of multiple sclerosis. J Cell Mol Med 2008;12(4):1087-93
  • Han MH, Hwang SI, Roy DB, et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 2008;451(7182):1076-81
  • Rosenling T, Attali A, Luider TM, Bischoff R. The experimental autoimmune encephalomyelitis model for proteomic biomarker studies: from rat to human. Clin Chim Acta 2011;412(11-12):812-22
  • Friese MA, Montalban X, Willcox N, et al. The value of animal models for drug development in multiple sclerosis. Brain 2006;129(Pt 8):1940-52
  • Raphael I, Mahesula S, Purkar A, et al. Microwave & Magnetic (M(2)) proteomics reveals CNS-specific protein expression waves that precede clinical symptoms of experimental autoimmune encephalomyelitis. Sci Rep 2014;4:6210
  • Bertolotto A, Sala A, Malucchi S, et al. Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies. J Neurol Neurosurg Psychiatry 2004;75(9):1294-9
  • Gerson B, Cohen SR, Gerson IM, Guest GH. Myelin basic protein, oligoclonal bands, and IgG in cerebrospinal fluid as indicators of multiple sclerosis. Clin Chem 1981;27(12):1974-7
  • Lamers KJ, Uitdehaag BM, Hommes OR, et al. The short-term effect of an immunosuppressive treatment on CSF myelin basic protein in chronic progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 1988;51(10):1334-7
  • Greene DN, Schmidt RL, Wilson AR, et al. Cerebrospinal fluid myelin basic protein is frequently ordered but has little value: a test utilization study. Am J Clin Pathol 2012;138(2):262-72
  • Celet B, Akman-Demir G, Serdaroglu P, et al. Anti-alpha B-crystallin immunoreactivity in inflammatory nervous system diseases. J Neurol 2000;247(12):935-9
  • Harada A, Oguchi K, Okabe S, et al. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 1994;369(6480):488-91

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