REFERENCES
1. Comabella M, Montalban X. Body fluid biomarkers in multiple sclerosis. Lancet Neurol 2014;13:113-26.
2. Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol 2017;16:661-76.
3. Teunissen CE, Malekzadeh A, Leurs C, Bridel C, Killestein J. Body fluid biomarkers for multiple sclerosis--the long road to clinical application. Nat Rev Neurol 2015;11:585-96.
5. Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation 2019;16:272.
6. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278-85.
7. FDA News Release. FDA approves new oral drug to treat multiple sclerosis. Available from: http://www.fda.gov/news-events/press-announcements/fda-approves-new-oral-drug-treat-multiple-sclerosis. [Last accessed on 2 Jul 2020].
8. FDA News Release. FDA approves new drug to treat multiple sclerosis. Available from: http://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-multiple-sclerosis. [Last accessed on 2 Jul 2020].
9. Comi G. Induction vs. escalating therapy in multiple sclerosis: practical implications. Neurol Sci 2008;29 Suppl 2:S253-5.
10. Giovannoni G, Tomic D, Bright JR, Havrdová E. “No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis. Mult Scler 2017;23:1179-87.
11. Håkansson I, Tisell A, Cassel P, Blennow K, Zetterberg H, et al. Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis. J Neuroinflammation 2018;15:209.
12. Pandit L. No evidence of disease activity (NEDA) in multiple sclerosis - shifting the goal posts. Ann Indian Acad Neurol 2019;22:261-3.
13. FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK338448/. [Last accessed on 2 Jul 2020].
14. Rush CA, MacLean HJ, Freedman MS. Aggressive multiple sclerosis: proposed definition and treatment algorithm. Nat Rev Neurol 2015;11:379-89.
15. Johanson CE, Duncan JA 3rd, Klinge PM, Brinker T, Stopa EG, et al. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 2008;5:10.
16. 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;84:909-14.
17. Imrell K, Landtblom AM, Hillert J, Masterman T. Multiple sclerosis with and without CSF bands: clinically indistinguishable but immunogenetically distinct. Neurology 2006;67:1062-4.
18. Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994;57:897-902.
19. Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 2005;62:865-70.
20. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018;17:162-73.
21. Schwenkenbecher P, Wurster U, Konen FF, Gingele S, Sühs KW, et al. Impact of the McDonald criteria 2017 on early diagnosis of relapsing-remitting multiple sclerosis. Front Neurol 2019;10:188.
22. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-31.
23. McDonald WI, Compston A, Edan G, Goodkin D, Hartung P, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121-7.
24. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.”. Ann Neurol 2005;58:840-6.
25. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292-302.
26. Sandberg-Wollheim M, Olsson T. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Yes. Mult Scler 2013;19:714-6.
27. Arrambide G, Tintore M, Espejo C, Auger C, Castillo M, et al. The value of oligoclonal bands in the multiple sclerosis diagnostic criteria. Brain 2018;141:1075-84.
28. Tintoré M, Rovira A, Brieva L, Grivé E, Jardí R, et al. Isolated demyelinating syndromes: comparison of CSF oligoclonal bands and different MR imaging criteria to predict conversion to CDMS. Mult Scler 2001;7:359-63.
29. Tintoré M, Rovira A, Río J, Tur C, Pelayo R, et al. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology 2008;70:1079-83.
30. Boyko A. Radiologically isolated syndrome with oligoclonal bands in CSF (RIS + OCB) can be classified as high MS risk group. Mult Scler 2020;26:869-70.
31. Makhani N, Lebrun C, Siva A, Narula S, Wassmer E, et al; Observatoire Francophone de la Sclérose en Plaques (OFSEP), Société Francophone de la Sclérose en Plaques (SFSEP), the Radiologically Isolated Syndrome Consortium (RISC) and the Pediatric Radiologically Isolated Syndrome Consortium (PARIS). Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome. Mult Scler J Exp Transl Clin 2019;5:2055217319836664.
32. Matute-Blanch C, Villar LM, Álvarez-Cermeño JC, Rejdak K, Evdoshenko E, et al. Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome. Brain 2018;141:1085-93.
33. Pryce G, Baker D. Oligoclonal bands in multiple sclerosis; Functional significance and therapeutic implications. Does the specificity matter? Mult Scler Relat Disord 2018;25:131-7.
34. Rejdak K, Stelmasiak Z, Grieb P. Cladribine induces long lasting oligoclonal bands disappearance in relapsing multiple sclerosis patients: 10-year observational study. Mult Scler Relat Disord 2019;27:117-20.
35. Mancuso R, Franciotta D, Rovaris M, Caputo D, Sala A, et al. Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: a longitudinal study. Mult Scler 2014;20:1900-3.
36. von Glehn F, Farias AS, de Oliveira AC, Damasceno A, Longhini AL, et al. Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients. Mult Scler 2012;18:1038-41.
37. Harrer A, Tumani H, Niendorf S, Lauda F, Geis C, et al. Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy. Mult Scler 2013;19:1209-12.
38. Koch M, Heersema D, Mostert J, Teelken A, De Keyser J. Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis. Eur J Neurol 2007;14:797-800.
39. Link H, Tibbling G. Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 1977;37:397-401.
40. Mayringer I, Timeltaler B, Deisenhammer F. Correlation between the IgG index, oligoclonal bands in CSF, and the diagnosis of demyelinating diseases. Eur J Neurol 2005;12:527-30.
41. Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol 2006;180:17-28.
42. Lefvert AK, Link H. IgG production within the central nervous system: a critical review of proposed formulae. Ann Neurol 1985;17:13-20.
43. Senel M, Tumani H, Lauda F, Presslauer S, Mojib-Yezdani R, et al. Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis. PLoS One 2014;9:e88680.
44. Izquierdo G, Angulo S, Garcia-Moreno JM, Gamero MA, Navarro G, et al. Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients. Acta Neurol Scand 2002;105:158-63.
45. Klein A, Selter RC, Hapfelmeier A, Berthele A, Müller-Myhsok B, et al. CSF parameters associated with early MRI activity in patients with MS. Neurol Neuroimmunol Neuroinflamm 2019;6:e573.
46. Gastaldi M, Zardini E, Franciotta D. An update on the use of cerebrospinal fluid analysis as a diagnostic tool in multiple sclerosis. Expert Rev Mol Diagn 2017;17:31-46.
47. Hegen H, Walde J, Milosavljevic D, Aboulenein-Djamshidian F, Senel M, et al. Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis. Clin Chem Lab Med 2019;57:1574-86.
48. Kaplan B, Aizenbud BM, Golderman S, Yaskariev R, Sela BA. Free light chain monomers in the diagnosis of multiple sclerosis. J Neuroimmunol 2010;229:263-71.
49. Hassan-Smith G, Durant L, Tsentemeidou A, Assi LK, Faint JM, et al. High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis. J Neuroimmunol 2014;276:175-9.
50. Desplat-Jégo S, Feuillet L, Pelletier J, Bernard D, Chérif AA, et al. Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry. J Clin Immunol 2005;25:338-45.
51. Duranti F, Pieri M, Centonze D, Buttari F, Bernardini S, et al. Determination of κFLC and κ Index in cerebrospinal fluid: a valid alternative to assess intrathecal immunoglobulin synthesis. J Neuroimmunol 2013;263:116-20.
52. Zeman D, Kušnierová P, Bartoš V, Hradílek P, Kurková B, et al. Quantitation of free light chains in the cerebrospinal fluid reliably predicts their intrathecal synthesis. Ann Clin Biochem 2016;53:174-6.
53. Pieri M, Storto M, Pignalosa S, Zenobi R, Buttari F, et al. KFLC index utility in multiple sclerosis diagnosis: further confirmation. J Neuroimmunol 2017;309:31-3.
54. Crespi I, Vecchio D, Serino R, Saliva E, Virgilio E, et al. K index is a reliable marker of intrathecal synthesis, and an alternative to IgG index in multiple sclerosis diagnostic work-up. J Clin Med 2019;8:446.
55. Puthenparampil M, Altinier S, Stropparo E, Zywicki S, Poggiali D, et al. Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination. Mult Scler Relat Disord 2018;25:241-5.
56. Gaetani L, Di Carlo M, Brachelente G, Valletta F, Eusebi P, et al. Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis. J Neuroimmunol 2020;339:577108.
57. Gurtner KM, Shosha E, Bryant SC, Andreguetto BD, Murray DL, et al. CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes. Clin Chem Lab Med 2018;56:1071-80.
58. Presslauer S, Milosavljevic D, Huebl W, Aboulenein-Djamshidian F, Krugluger W, et al. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: a multicenter study. Mult Scler 2016;22:502-10.
59. Leurs CE, Twaalfhoven H, Lissenberg-Witte BI, van Pesch V, Dujmovic I, et al. Kappa free light chains is a valid tool in the diagnostics of MS: a large multicenter study. Mult Scler 2020;26:912-23.
60. Makshakov G, Nazarov V, Kochetova O, Surkova E, Lapin S, et al. Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis. PLoS One 2015;10:e0143375.
61. Presslauer S, Milosavljevic D, Huebl W, Parigger S, Schneider-Koch G, et al. Kappa free light chains: diagnostic and prognostic relevance in MS and CIS. PLoS One 2014;9:e89945.
62. Presslauer S, Milosavljevic D, Brücke T, Bayer P, Hübl W. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol 2008;255:1508-14.
63. Ferraro D, Trovati A, Bedin R, Natali P, Franciotta D, et al. Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple sclerosis. Eur J Neurol 2020;27:461-7.
64. Vecchio D, Crespi I, Virgilio E, Naldi P, Campisi MP, et al. Kappa free light chains could predict early disease course in multiple sclerosis. Mult Scler Relat Disord 2019;30:81-4.
65. Rinker JR 2nd, Trinkaus K, Cross AH. Elevated CSF free kappa light chains correlate with disability prognosis in multiple sclerosis. Neurology 2006;67:1288-90.
66. Rudick RA, Medendorp SV, Namey M, Boyle S, Fischer J. Multiple sclerosis progression in a natural history study: predictive value of cerebrospinal fluid free kappa light chains. Mult Scler 1995;1:150-5.
67. Rathbone E, Durant L, Kinsella J, Parker AR, Hassan-Smith G, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry 2018;89:1044-9.
68. Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig 1992;70:28-37.
69. Tumani H, Tourtellotte WW, Peter JB, Felgenhauer K; The Optic Neuritis Study Group. Acute optic neuritis: combined immunological markers and magnetic resonance imaging predict subsequent development of multiple sclerosis. J Neurol Sci 1998;155:44-9.
70. Brettschneider J, Tumani H, Kiechle U, Muche R, Richards G, et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One 2009;4:e7638.
71. Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler 1998;4:111-7.
72. Hottenrott T, Schorb E, Fritsch K, Dersch R, Berger B, et al. The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central nervous system lymphoma and multiple sclerosis. J Neurol 2018;265:1106-14.
73. Jarius S, Eichhorn P, Franciotta D, Petereit HF, Akman-Demir G, et al. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature. J Neurol 2017;264:453-66.
74. Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F. B cells and multiple sclerosis. Lancet Neurol 2008;7:852-8.
75. Godec MS, Asher DM, Murray RS, Shin ML, Greenham LW, et al. Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol 1992;32:401-4.
76. Ibitoye R, Kemp K, Rice C, Hares K, Scolding N, et al. Oxidative stress-related biomarkers in multiple sclerosis: a review. Biomark Med 2016;10:889-902.
77. Smith KJ, Lassmann H. The role of nitric oxide in multiple sclerosis. Lancet Neurol 2002;1:232-41.
78. Yamashita T, Ando Y, Obayashi K, Uchino M, Ando M. Changes in nitrite and nitrate (NO2-/NO3-) levels in cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci 1997;153:32-4.
79. Miljkovic Dj, Drulovic J, Trajkovic V, Mesaros S, Dujmovic I, et al. Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients. Eur J Neurol 2002;9:413-8.
80. Yuceyar N, Taşkiran D, Sağduyu A. Serum and cerebrospinal fluid nitrite and nitrate levels in relapsing-remitting and secondary progressive multiple sclerosis patients. Clin Neurol Neurosurg 2001;103:206-11.
81. Giovannoni G, Heales S, Silver N, O’riordan J, Miller R, et al. Raised serum nitrate and nitrite levels in patients with multiple sclerosis. J Neurol Sci 1997;145:77-81.
82. Haghikia A, Kayacelebi AA, Beckmann B, Hanff E, Gold R, et al. Serum and cerebrospinal fluid concentrations of homoarginine, arginine, asymmetric and symmetric dimethylarginine, nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica. Amino Acids 2015;47:1837-45.
83. Giovannoni G, Silver NC, O’Riordan J, Miller RF, Heales SJ, et al. Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease. Mult Scler 1999;5:335-41.
84. Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, et al. Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. J Neurosci Res 2002;70:580-7.
85. Hua LL, Liu JS, Brosnan CF, Lee SC. Selective inhibition of human glial inducible nitric oxide synthase by interferon-beta: implications for multiple sclerosis. Ann Neurol 1998;43:384-7.
86. Danilov AI, Andersson M, Bavand N, Wiklund N, Olsson T, et al. Nitric oxide metabolite determinations reveal continuous inflammation in multiple sclerosis. J Neuroimmunol 2003;136:112-8.
87. Giovannoni G, Miller DH, Losseff NA, Sailer M, Lewellyn-Smith N, et al. Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis. J Neurol 2001;248:487-95.
88. Tavazzi B, Batocchi AP, Amorini AM, Nociti V, D’Urso S, et al. Serum metabolic profile in multiple sclerosis patients. Mult Scler Int 2011;2011:167156.
89. Svenningsson A, Petersson AS, Andersen O, Hansson GK. Nitric oxide metabolites in CSF of patients with MS are related to clinical disease course. Neurology 1999;53:1880-2.
90. Acar G, Idiman F, Idiman E, Kirkali G, Cakmakçi H, et al. Nitric oxide as an activity marker in multiple sclerosis. J Neurol 2003;250:588-92.
91. Sellebjerg F, Giovannoni G, Hand A, Madsen H, Jensen C, et al. Cerebrospinal fluid levels of nitric oxide metabolites predict response to methylprednisolone treatment in multiple sclerosis and optic neuritis. J Neuroimmunol 2002;125:198-203.
92. Rejdak K, Eikelenboom MJ, Petzold A, Thompson EJ, Stelmasiak Z, et al. CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis. Neurology 2004;63:1439-45.
93. Merry K, Dodds R, Littlewood A, Gowen M. Expression of osteopontin mRNA by osteoclasts and osteoblasts in modelling adult human bone. J Cell Sci 1993;104:1013-20.
94. Del Prete A, Scutera S, Sozzani S, Musso T. Role of osteopontin in dendritic cell shaping of immune responses. Cytokine Growth Factor Rev 2019;50:19-28.
95. Murugaiyan G, Mittal A, Weiner HL. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 2008;181:7480-8.
96. Braitch M, Constantinescu CS. The role of osteopontin in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Inflamm Allergy Drug Targets 2010;9:249-56.
97. Sato W, Tomita A, Ichikawa D, Lin Y, Kishida H, et al. CCR2(+)CCR5(+) T cells produce matrix metalloproteinase-9 and osteopontin in the pathogenesis of multiple sclerosis. J Immunol 2012;189:5057-65.
98. Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 2001;294:1731-5.
99. Sinclair C, Mirakhur M, Kirk J, Farrell M, McQuaid S. Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays. Neuropathol Appl Neurobiol 2005;31:292-303.
100. Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L. Elevated osteopontin levels in active relapsing-remitting multiple sclerosis. Ann Neurol 2003;53:819-22.
101. Agah E, Zardoui A, Saghazadeh A, Ahmadi M, Tafakhori A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One 2018;13:e0190252.
102. Shimizu Y, Ota K, Ikeguchi R, Kubo S, Kabasawa C, et al. Plasma osteopontin levels are associated with disease activity in the patients with multiple sclerosis and neuromyelitis optica. J Neuroimmunol 2013;263:148-51.
103. Chowdhury SA, Lin J, Sadiq SA. Specificity and correlation with disease activity of cerebrospinal fluid osteopontin levels in patients with multiple sclerosis. Arch Neurol 2008;65:232-5.
104. Comabella M, Pericot I, Goertsches R, Nos C, Castillo M, et al. Plasma osteopontin levels in multiple sclerosis. J Neuroimmunol 2005;158:231-9.
105. Vogt MH, Floris S, Killestein J, Knol DL, Smits M, et al. Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients. J Neuroimmunol 2004;155:155-60.
106. Wen SR, Liu GJ, Feng RN, Gong FC, Zhong H, et al. Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2012;244:94-6.
107. Kivisäkk P, Healy BC, Francois K, Gandhi R, Gholipour T, et al. Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development. Mult Scler 2014;20:438-44.
108. Braitch M, Nunan R, Niepel G, Edwards LJ, Constantinescu CS. Increased osteopontin levels in the cerebrospinal fluid of patients with multiple sclerosis. Arch Neurol 2008;65:633-5.
109. Vogt MH, ten Kate J, Drent RJ, Polman CH, Hupperts R. Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers. Mult Scler 2010;16:443-9.
110. Börnsen L, Khademi M, Olsson T, Sørensen PS, Sellebjerg F. Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis. Mult Scler 2011;17:32-42.
111. Szalardy L, Zadori D, Simu M, Bencsik K, Vecsei L, et al. Evaluating biomarkers of neuronal degeneration and neuroinflammation in CSF of patients with multiple sclerosis-osteopontin as a potential marker of clinical severity. J Neurol Sci 2013;331:38-42.
112. Dianzani C, Vecchio D, Clemente N, Chiocchetti A, Martinelli Boneschi F, et al. Untangling extracellular proteasome-osteopontin circuit dynamics in multiple sclerosis. Cells 2019;8:262.
113. Runia TF, van Meurs M, Nasserinejad K, Hintzen RQ. No evidence for an association of osteopontin plasma levels with disease activity in multiple sclerosis. Mult Scler 2014;20:1670-1.
114. Zhao Q, Cheng W, Xi Y, Cao Z, Xu Y, et al. IFN-β regulates Th17 differentiation partly through the inhibition of osteopontin in experimental autoimmune encephalomyelitis. Mol Immunol 2018;93:20-30.
115. Hong J, Hutton GJ. Regulatory effects of interferon-β on osteopontin and interleukin-17 expression in multiple sclerosis. J Interferon Cytokine Res 2010;30:751-7.
116. Iaffaldano P, Ruggieri M, Viterbo RG, Mastrapasqua M, Trojano M. The improvement of cognitive functions is associated with a decrease of plasma Osteopontin levels in Natalizumab treated relapsing multiple sclerosis. Brain Behav Immun 2014;35:176-81.
117. Mas A, Martínez A, de las Heras V, Bartolomé M, de la Concha EG, et al. The 795CT polymorphism in osteopontin gene is not associated with multiple sclerosis in a Spanish population. Mult Scler 2007;13:250-2.
118. Biernacka-Lukanty J, Michalowska-Wender G, Michalak S, Raczak B, Kozubski W, et al. Polymorphism of the osteopontin gene and clinical course of multiple sclerosis in the Polish population. Folia Neuropathol 2015;53:343-6.
119. Caillier S, Barcellos LF, Baranzini SE, Swerdlin A, Lincoln RR, et al; Multiple Sclerosis Genetics Group. Osteopontin polymorphisms and disease course in multiple sclerosis. Genes Immun 2003;4:312-5.
120. Chiocchetti A, Comi C, Indelicato M, Castelli L, Mesturini R, et al. Osteopontin gene haplotypes correlate with multiple sclerosis development and progression. J Neuroimmunol 2005;163:172-8.
121. Comi C, Cappellano G, Chiocchetti A, Orilieri E, Buttini S, et al. The impact of osteopontin gene variations on multiple sclerosis development and progression. Clin Dev Immunol 2012;2012:212893.
122. Londoño AC, Mora CA. Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis. F1000Res 2018;7:514.
123. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004;14:164-74.
124. Bagaeva LV, Rao P, Powers JM, Segal BM. CXC chemokine ligand 13 plays a role in experimental autoimmune encephalomyelitis. J Immunol 2006;176:7676-85.
125. Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 2006;129:200-11.
126. Bai Z, Chen D, Wang L, Zhao Y, Liu T, et al. Cerebrospinal fluid and blood cytokines as biomarkers for multiple sclerosis: a systematic review and meta-analysis of 226 studies with 13,526 multiple sclerosis patients. Front Neurosci 2019;13:1026.
127. Sellebjerg F, Börnsen L, Khademi M, Krakauer M, Olsson T, et al. Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology 2009;73:2003-10.
128. Khademi M, Kockum I, Andersson ML, Iacobaeus E, Brundin L, et al. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult Scler 2011;17:335-43.
129. Irani DN. Regulated Production of CXCL13 within the Central Nervous System. J Clin Cell Immunol 2016;7:460.
130. Brettschneider J, Czerwoniak A, Senel M, Fang L, Kassubek J, et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One 2010;5:e11986.
131. Piccio L, Naismith RT, Trinkaus K, Klein RS, Parks BJ, et al. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010;67:707-14.
132. Romme Christensen J, Ratzer R, Börnsen L, Lyksborg M, Garde E, et al. Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of-concept trial. Neurology 2014;82:1499-507.
133. Rempe RG, Hartz AMS, Bauer B. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. J Cereb Blood Flow Metab 2016;36:1481-507.
134. Wang Y, Wu H, Wu X, Bian Z, Gao Q. Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression. PLoS One 2014;9:e96678.
135. Moon SK, Cha BY, Kim CH. ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: involvement of the ras dependent pathway. J Cell Physiol 2004;198:417-27.
136. Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Current Biology 1999;9:1441-7.
137. Woo MS, Park JS, Choi IY, Kim WK, Kim HS. Inhibition of MMP-3 or -9 suppresses lipopolysaccharide-induced expression of proinflammatory cytokines and iNOS in microglia. J Neurochem 2008;106:770-80.
138. Agrawal S, Anderson P, Durbeej M, van Rooijen N, Ivars F, et al. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 2006;203:1007-19.
139. Nygårdas PT, Hinkkanen AE. Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord correlates with the severity of experimental autoimmune encephalomyelitis. Clin Exp Immunol 2002;128:245-54.
140. Buhler LA, Samara R, Guzman E, Wilson CL, Krizanac-Bengez L, et al. Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis. BMC Neurosci 2009;10:17.
141. Fainardi E, Castellazzi M, Tamborino C, Trentini A, Manfrinato MC, et al. Potential relevance of cerebrospinal fluid and serum levels and intrathecal synthesis of active matrix metalloproteinase-2 (MMP-2) as markers of disease remission in patients with multiple sclerosis. Mult Scler 2009;15:547-54.
142. Trentini A, Castellazzi M, Cervellati C, Manfrinato MC, Tamborino C, et al. Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients. Dis Markers 2016;2016:3672353.
143. Liuzzi GM, Trojano M, Fanelli M, Avolio C, Fasano A, et al. Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis. Mult Scler 2002;8:222-8.
144. Lee MA, Palace J, Stabler G, Ford J, Gearing A, et al. Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain 1999;122:191-7.
145. Lichtinghagen R, Seifert T, Kracke A, Marckmann S, Wurster U, et al. Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood cells of patients with multiple sclerosis. J Neuroimmunol 1999;99:19-26.
146. Waubant E, Goodkin DE, Gee L, Bacchetti P, Sloan R, et al. Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 1999;53:1397-401.
147. Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, 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;12:294-301.
148. Leppert D, Ford J, Stabler G, Grygar C, Lienert C, et al. Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 1998;121:2327-34.
149. Benesová Y, Vasku A, Novotná H, Litzman J, Stourac P, et al. Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis. Mult Scler 2009;15:316-22.
150. Lindberg RL, De Groot CJ, Montagne L, Freitag P, van der Valk P, et al. The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 2001;124:1743-53.
151. Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, et al. Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol 1997;23:406-15.
152. Galboiz Y, Shapiro S, Lahat N, Rawashdeh H, Miller A. Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferon-beta therapy in relapsing and secondary-progressive multiple sclerosis patients. Ann Neurol 2001;50:443-51.
153. Bernal F, Elias B, Hartung HP, Kieseier BC. Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients. Mult Scler 2009;15:721-7.
154. Comabella M, Río J, Espejo C, Ruiz de Villa M, Al-Zayat H, et al. Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis. Clin Immunol 2009;130:145-50.
155. Balasa R, Bianca C, Septimiu V, Iunius S, Adina H, et al. The matrix metalloproteinases panel in multiple sclerosis patients treated with Natalizumab: a possible answer to Natalizumab non-responders. CNS Neurol Disord Drug Targets 2018;17:464-72.
156. Castellazzi M, Bellini T, Trentini A, Delbue S, Elia F, et al. Serum gelatinases levels in multiple sclerosis patients during 21 months of Natalizumab therapy. Dis Markers 2016;2016:8434209.
157. Fissolo N, Pignolet B, Matute-Blanch C, Triviño JC, Miró B, et al; Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment (BIONAT)m Best EScalation Treatment in Multiple Sclerosis (BEST-MS), and the Société Francophone de la Sclérose En Plaques (SFSEP) Network. Matrix metalloproteinase 9 is decreased in natalizumab-treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy. Ann Neurol 2017;82:186-95.
158. Cohen SR, Brooks BR, Herndon RM, McKhann GM. A diagnostic index of active demyelination: myelin basic protein in cerebrospinal fluid. Ann Neurol 1980;8:25-31.
159. Whitaker JN, Lisak RP, Bashir RM, Fitch OH, Seyer JM, et al. Immunoreactive myelin basic protein in the cerebrospinal fluid in neurological disorders. Ann Neurol 1980;7:58-64.
160. Stadelmann C, Timmler S, Barrantes-Freer A, Simons M. Myelin in the central nervous system: structure, function, and pathology. Physiol Rev 2019;99:1381-431.
161. Whitaker JN. Myelin basic protein in cerebrospinal fluid and other body fluids. Mult Scler 1998;4:16-21.
162. Meinl E, Hohlfeld R. Immunopathogenesis of multiple sclerosis: MBP and beyond. Clin Exp Immunol 2002;128:395-7.
163. Olsson T, Sun J, Hillert J, Höjeberg B, Ekre HP, et al. Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis. Eur J Immunol 1992;22:1083-7.
164. Kim YC, Zhang AH, Yoon J, Culp WE, Lees JR, et al. Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells. J Autoimmun 2018;92:77-86.
165. Whitaker JN. Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis. Neurology 1977;27:911-20.
166. Sellebjerg F, Christiansen M, Nielsen PM, Frederiksen JL. Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis. Mult Scler 1998;4:475-9.
167. Noppe M, Crols R, Andries D, Lowenthal A. Determination in human cerebrospinal fluid of glial fibrillary acidic protein, S-100 and myelin basic protein as indices of non-specific or specific central nervous tissue pathology. Clinica Chimica Acta 1986;155:143-50.
168. Lamers KJ, de Reus HP, Jongen PJ. Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis. Mult Scler 1998;4:124-6.
169. Barkhof F, Frequin ST, Hommes OR, Lamers K, Scheltens P, 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;42:63-7.
170. Zhou Y, Simpson S Jr, Charlesworth JC, van der Mei I, Lucas RM, et al; AUSLONG Investigators Group. Variation within MBP gene predicts disease course in multiple sclerosis. Brain Behav 2017;7:e00670.
171. Belogurov A Jr, Zakharov K, Lomakin Y, Surkov K, Avtushenko S, et al. CD206-targeted liposomal myelin basic protein peptides in patients with multiple sclerosis resistant to first-line disease-modifying therapies: a first-in-human, proof-of-concept dose-escalation study. Neurotherapeutics 2016;13:895-904.
172. Warren KG, Catz I, Ferenczi LZ, Krantz MJ. Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. Eur J Neurol 2006;13:887-95.
173. Establish Tolerance In MS With Peptide-Coupled, Peripheral Blood Mononuclear Cells (ETIMS). Available from: https://clinicaltrials.gov/ct2/show/NCT01414634. [Last accessed on 7 Jul 2020].
174. Safety, Tolerability, and Effectiveness of CGP77116 in Patients With Multiple Sclerosis (MS). Available from: https://clinicaltrials.gov/ct2/show/NCT00001781. [Last accessed on 7 Jul 2020].
175. Tumani H, Hartung HP, Hemmer B, Teunissen C, Deisenhammer F, et al; BioMS Study Group. Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol Dis 2009;35:117-27.
176. Zołtowska A, Stepiński J, Lewko B, Serkies K, Zamorska B, et al. Neural cell adhesion molecule in breast, colon and lung carcinomas. Arch Immunol Ther Exp (Warsz) 2001;49:171-4.
178. Massaro AR, Sbriccoli A, Tonali P. Reactive astrocytes within the acute plaques of multiple sclerosis are PSA-NCAM positive. Neurol Sci 2002;23:255-6.
179. Le Gal La Salle G, Rougon G, Valin A. The embryonic form of neural cell surface molecule (E-NCAM) in the rat hippocampus and its reexpression on glial cells following kainic acid- induced status epilepticus. J Neurosci 1992;12:872-82.
180. Gnanapavan S, Grant D, Illes-Toth E, Lakdawala N, Keir G, et al. Neural cell adhesion molecule--description of a CSF ELISA method and evidence of reduced levels in selected neurological disorders. J Neuroimmunol 2010;225:118-22.
181. Axelsson M, Dubuisson N, Novakova L, Malmeström C, Giovannoni G, et al. Cerebrospinal fluid NCAM levels are modulated by disease-modifying therapies. Acta Neurol Scand 2019;139:422-7.
182. Massaro AR, Albrechtsen M, Bock E. N-CAM in cerebrospinal fluid: a marker of synaptic remodelling after acute phases of multiple sclerosis? Ital J Neurol Sci 1987;Suppl 6:85-8.
183. Massaro AR. Are there indicators of remyelination in blood or CSF of multiple sclerosis patients? Mult Scler 1998;4:228-31.
184. Paul A, Comabella M, Gandhi R. Biomarkers in Multiple Sclerosis. Cold Spring Harb Perspect Med 2019;9:a029058.
185. Correale J, Fiol M. Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis. Mult Scler 2011;17:521-31.
186. Kanneganti M, Kamba A, Mizoguchi E. Role of chitotriosidase (chitinase 1) under normal and disease conditions. J Epithel Biol Pharmacol 2012;5:1-9.
187. De Fino C, Lucchini M, Lucchetti D, Nociti V, Losavio FA, et al. The predictive value of CSF multiple assay in multiple sclerosis: a single center experience. Mult Scler Relat Disord 2019;35:176-81.
188. Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, et al. Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem 2017;141:296-304.
189. Sellebjerg F, Börnsen L, Ammitzbøll C, Nielsen JE, Vinther-Jensen T, et al. Defining active progressive multiple sclerosis. Mult Scler 2017;23:1727-35.
190. Comabella M, Fernández M, Martin R, Rivera-Vallvé S, Borrás E, et al. Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 2010;133:1082-93.
191. Borràs E, Cantó E, Choi M, Maria Villar L, Álvarez-Cermeño JC, et al. Protein-based classifier to predict conversion from clinically isolated syndrome to multiple sclerosis. Mol Cell Proteomics 2016;15:318-28.
192. Cantó E, Tintoré M, Villar LM, Costa C, Nurtdinov R, et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 2015;138:918-31.
193. Matute-Blanch C, Río J, Villar LM, Midaglia L, Malhotra S, et al. Chitinase 3-like 1 is associated with the response to interferon-beta treatment in multiple sclerosis. J Neuroimmunol 2017;303:62-5.
194. Lovett-Racke AE, Yang Y, Racke MK. Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim Biophys Acta 2011;1812:246-51.
195. Longbrake EE, Racke MK. Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Rev Neurother 2009;9:319-21.
196. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-8.
197. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-gort R, et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008;7:796-804.
198. Matusevicius D, Kivisäkk P, He B, Kostulas N, Ozenci V, et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 1999;5:101-4.
199. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002;8:500-8.
200. Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 2009;132:3329-41.
201. Havrdová E, Belova A, Goloborodko A, Tisserant A, Wright A, et al. Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study. J Neurol 2016;263:1287-95.
202. Ishizu T, Osoegawa M, Mei FJ, Kikuchi H, Tanaka M, et al. Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 2005;128:988-1002.
203. Rossi S, Motta C, Studer V, Barbieri F, Buttari F, et al. Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration. Mult Scler 2014;20:304-12.
204. Trenova AG, Slavov GS, Draganova-Filipova MN, Mateva NG, Manova MG, et al. Circulating levels of interleukin-17A, tumor necrosis factor-alpha, interleukin-18, interleukin-10, and cognitive performance of patients with relapsing-remitting multiple sclerosis. Neurol Res 2018;40:153-9.
205. Pegoretti V, Baron W, Laman JD, Eisel ULM. Selective Modulation of TNF-TNFRs Signaling: insights for multiple sclerosis treatment. Front Immunol 2018;9:925.
206. Caminero A, Comabella M, Montalban X. Tumor necrosis factor alpha (TNF-α), anti-TNF-α and demyelination revisited: an ongoing story. J Neuroimmunol 2011;234:1-6.
207. Brambilla R, Ashbaugh JJ, Magliozzi R, Dellarole A, Karmally S, et al. Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination. Brain 2011;134:2736-54.
208. Ng LG, Sutherland AP, Newton R, Qian F, Cachero TG, et al. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol 2004;173:807-17.
209. Kannel K, Alnek K, Vahter L, Gross-Paju K, Uibo R, et al. Changes in blood B cell-activating factor (BAFF) levels in multiple sclerosis: a sign of treatment outcome. PLoS One 2015;10:e0143393.
210. Friede RL, Samorajski T. Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat Rec 1970;167:379-87.
211. Varhaug KN, Torkildsen Ø, Myhr KM, Vedeler CA. Neurofilament light chain as a biomarker in multiple sclerosis. Front Neurol 2019;10:338.
212. Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelsø C. Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem 1996;67:2013-8.
213. De Schaepdryver M, Jeromin A, Gille B, Claeys KG, Herbst V, et al. Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2018;89:367-73.
214. Fyfe I. Alzheimer disease: neurofilament light in the blood marks Alzheimer degeneration. Nat Rev Neurol 2017;13:257.
215. Meeter LH, Dopper EG, Jiskoot LC, Sanchez-Valle R, Graff C, et al. Neurofilament light chain: a biomarker for genetic frontotemporal dementia. Ann Clin Transl Neurol 2016;3:623-36.
216. Mages B, Aleithe S, Altmann S, Blietz A, Nitzsche B, et al. Impaired neurofilament integrity and neuronal morphology in different models of focal cerebral ischemia and human stroke tissue. Front Cell Neurosci 2018;12:161.
217. Byrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, et al. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol 2017;16:601-9.
218. Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, et al; the NFL Group. Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. JAMA Neurol 2019;76:1035-48.
219. Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, et al. Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm 2016;3:e271.
220. Novakova L, Zetterberg H, Sundström P, Axelsson M, Khademi M, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology 2017;89:2230-7.
221. Kuhle J, Barro C, Disanto G, Mathias A, Soneson C, et al. Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler 2016;22:1550-9.
222. Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med 2016;54:1655-61.
223. Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, et al; Swiss Multiple Sclerosis Cohort Study Group. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017;81:857-70.
224. Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, et al. Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 2009;72:1322-9.
225. Kuhle J, Leppert D, Petzold A, Regeniter A, Schindler C, et al. Neurofilament heavy chain in CSF correlates with relapses and disability in multiple sclerosis. Neurology 2011;76:1206-13.
226. Norgren N, Sundström P, Svenningsson A, Rosengren L, Stigbrand T, et al. Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology 2004;63:1586-90.
227. Cai L, Huang J. Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study. Neuropsychiatr Dis Treat 2018;14:2241-54.
228. Martin SJ, McGlasson S, Hunt D, Overell J. Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case-control studies. J Neurol Neurosurg Psychiatry 2019;90:1059-67.
229. Kuhle J, Nourbakhsh B, Grant D, Morant S, Barro C, et al. Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology 2017;88:826-31.
230. Quintana E, Coll C, Salavedra-Pont J, Muñoz-San Martín M, Robles-Cedeño R, et al. Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain. Eur J Neurol 2018;25:1189-91.
231. Kuhle J, Plavina T, Barro C, Disanto G, Sangurdekar D, et al. Neurofilament light levels are associated with long-term outcomes in multiple sclerosis. Mult Scler 2019; doi: 10.1177/1352458519885613.
232. Ferraro D, Guicciardi C, De Biasi S, Pinti M, Bedin R, et al. Plasma neurofilaments correlate with disability in progressive multiple sclerosis patients. Acta Neurol Scand 2020;141:16-21.
233. Disanto G, Adiutori R, Dobson R, Martinelli V, Dalla Costa G, et al; International Clinically Isolated Syndrome Study Group. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome. J Neurol Neurosurg Psychiatry 2016;87:126-9.
234. Martínez MA, Olsson B, Bau L, Matas E, Cobo Calvo Á, et al. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Mult Scler 2015;21:550-61.
235. Modvig S, Degn M, Roed H, Sørensen TL, Larsson HB, et al. Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis. Mult Scler 2015;21:1761-70.
236. Siller N, Kuhle J, Muthuraman M, Barro C, Uphaus T, et al. Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis. Mult Scler 2019;25:678-86.
237. Varhaug KN, Barro C, Bjørnevik K, Myhr KM, Torkildsen Ø, et al. Neurofilament light chain predicts disease activity in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm 2018;5:e422.
238. Chitnis T, Gonzalez C, Healy BC, Saxena S, Rosso M, et al. Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis. Ann Clin Transl Neurol 2018;5:1478-91.
239. Axelsson M, Malmeström C, Gunnarsson M, Zetterberg H, Sundström P, et al. Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis. Mult Scler 2014;20:43-50.
240. Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, et al. Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis. Mult Scler 2017;23:62-71.
241. Kuhle J, Malmeström C, Axelsson M, Plattner K, Yaldizli O, et al. Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis. Acta Neurol Scand 2013;128:e33-6.
242. Gunnarsson M, Malmeström C, Axelsson M, Sundström P, Dahle C, et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 2011;69:83-9.
243. Akgün K, Kretschmann N, Haase R, Proschmann U, Kitzler HH, et al. Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS. Neurol Neuroimmunol Neuroinflamm 2019;6:e555.
244. Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (TREAT-MS). Available from: https://clinicaltrials.gov/ct2/show/NCT03500328. [Last accessed on 9 Jul 2020].
245. Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: the immune system in health and disease. 5th edition. New York: Garland Science; 2001. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27162/. [Last accessed on 9 Jul 2020].
246. Sharief MK, Keir G, Thompson EJ. Intrathecal synthesis of IgM in neurological diseases: a comparison between detection of oligoclonal bands and quantitative estimation. J Neurol Sci 1990;96:131-42.
247. Villar LM, Masjuan J, González-Porqué P, Plaza J, Sádaba MC, et al. Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis. Ann Neurol 2003;53:222-6.
248. Mandrioli J, Sola P, Bedin R, Gambini M, Merelli E. A multifactorial prognostic index in multiple sclerosis. Cerebrospinal fluid IgM oligoclonal bands and clinical features to predict the evolution of the disease. J Neurol 2008;255:1023-31.
249. Magraner MJ, Bosca I, Simó-Castelló M, García-Martí G, Alberich-Bayarri A, et al. Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes. Neuroradiology 2012;54:5-12.
250. Villar LM, Sádaba MC, Roldán E, Masjuan J, González-Porqué P, et al. Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest 2005;115:187-94.
251. Durante L, Zaaraoui W, Rico A, Crespy L, Wybrecht D, et al. Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual. Mult Scler 2012;18:587-91.
252. Boscá I, Magraner MJ, Coret F, Alvarez-Cermeño JC, Simó-Castelló M, et al. The risk of relapse after a clinically isolated syndrome is related to the pattern of oligoclonal bands. J Neuroimmunol 2010;226:143-6.
253. Ferraro D, Simone AM, Bedin R, Galli V, Vitetta F, et al. Cerebrospinal fluid oligoclonal IgM bands predict early conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome. J Neuroimmunol 2013;257:76-81.
254. Espiño M, Abraira V, Arroyo R, Bau L, Cámara C, et al. Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice. Clin Chim Acta 2015;438:67-9.
255. Sola P, Mandrioli J, Simone AM, Ferraro D, Bedin R, et al. Primary progressive versus relapsing-onset multiple sclerosis: presence and prognostic value of cerebrospinal fluid oligoclonal IgM. Mult Scler 2011;17:303-11.
256. Bosca I, Villar LM, Coret F, Magraner MJ, Simó-Castelló M, et al. Response to interferon in multiple sclerosis is related to lipid-specific oligoclonal IgM bands. Mult Scler 2010;16:810-5.
257. Selter RC, Biberacher V, Grummel V, Buck D, Eienbröker C, et al. Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients. Mult Scler 2013;19:1454-61.
258. Villar LM, García-Sánchez MI, Costa-Frossard L, Espiño M, Roldán E, et al. Immunological markers of optimal response to natalizumab in multiple sclerosis. Arch Neurol 2012;69:191-7.
259. Hol EM, Pekny M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol 2015;32:121-30.
260. Bélanger M, Magistretti PJ. The role of astroglia in neuroprotection. Dialogues Clin Neurosci 2009;11:281-95.
261. Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 2015;38:364-74.
262. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017;541:481-7.
263. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015;14:183-93.
264. Abdelhak A, Hottenrott T, Morenas-Rodríguez E, Suárez-Calvet M, Zettl UK, et al. Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker? Front Neurol 2019;10:280.
265. Rosengren L, Lycke J, Andersen O. Glial fibrillary acidic protein in CSF of multiple sclerosis patients: relation to neurological deficit. J Neurol Sci 1995;133:61-5.
266. Petzold A, Eikelenboom MJ, Gveric D, Keir G, Chapman M, et al. Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 2002;125:1462-73.
267. Axelsson M, Malmeström C, Nilsson S, Haghighi S, Rosengren L, et al. Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis. J Neurol 2011;258:882-8.
268. Högel H, Rissanen E, Barro C, Matilainen M, Nylund M, et al. Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity. Mult Scler 2020;26:210-9.
