Role of magnetic resonance imaging and immunotherapy in treating multiple sclerosis

Annual Review of Medicine

Volumn 56, Issue , 2005, Pages 273-302

  Zhang, Jingwu ^a,b   Hutton, George ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b INSTITUTE OF GEOLOGY AND GEOPHYSICS   (China)

Author keywords

Acetate; Glatiramer; Interferon beta; T lymphocytes

Indexed keywords

1 [5 CHLORO 2 [2 [4 (4 FLUOROBENZYL) 2 METHYL 1 PIPERAZINYL] 2 OXOETHOXY]PHENYL]UREA; ALEMTUZUMAB; ATM 027; BETA1A INTERFERON; CD4 ANTIGEN; CEP 151; CORTICOSTEROID; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; ESTRIOL; ESTROGEN; GADOLINIUM; GLATIRAMER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IDEC C28; IMMUNOMODULATING AGENT; INTERFERON BETA SERINE; IR 208; METHYLPREDNISOLONE; MINOCYCLINE; MYELIN BASIC PROTEIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; NATALIZUMAB; NEUROVAX; RECOMBINANT SOMATOMEDIN C; RILUZOLE; RITUXIMAB; SIMVASTATIN; T CELL VACCINE; T LYMPHOCYTE RECEPTOR PEPTIDE VACCINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VACCINE; VERY LATE ACTIVATION ANTIGEN 4;

BRAIN ATROPHY; CLINICAL TRIAL; DIAGNOSTIC VALUE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; GENETIC HETEROGENEITY; GENETIC SUSCEPTIBILITY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMAGE ENHANCEMENT; IMMUNOPHARMACOLOGY; IMMUNOREACTIVITY; IMMUNOTHERAPY; MULTIPLE SCLEROSIS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOGENESIS; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; PRIORITY JOURNAL; REVIEW; VACCINATION;

AUTOANTIBODIES; BRAIN; CLINICAL TRIALS; DRUGS, INVESTIGATIONAL; EPITOPES; FOLLOW-UP STUDIES; HUMANS; IMAGE ENHANCEMENT; IMMUNOTHERAPY; MAGNETIC RESONANCE IMAGING; MULTIPLE SCLEROSIS; SPINAL CORD;

EID: 14544303231     PISSN: 00664219     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.med.56.082103.104739     Document Type: Review

References (164)

1. Noseworthy JH, Lucchinetti C, Rodriguez M, et al. 2000. Multiple sclerosis. N. Engl. J. Med. 343:938-52
2. National Multiple Sclerosis Society. 2003. About MS. Who get MS? http://www.nationalmssociety.org/WHO%20ge ts%20MS.asp
3. Lublin FD, Reingold SC. 1996. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 46:907-11
4. Lucchinetti C, Brück W, Parisi J, et al. 2000. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47:707-17
5. Lassmann H, Ransohoff RM. 2004. The CD4-Th1 model for multiple sclerosis: a crucial reappraisal. Trends Immunol. 25: 132-37
6. Neuhaus O, Archelos JJ, Hartung H-P. 2003. Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. Trends Pharmacol. Sci. 24:131-37
7. Martin R, McFarland HF, McFarlin DE. 1992. Immunological aspects of demyelinating diseases. Annu. Rev. Immunol. 10: 153-87
8. + T-cell responses to human myelin protein-derived peptides. Proc. Natl. Acad. Sci. USA 91: 10859-63
9. Jurewicz A, Biddison WE, Antel JP. 1998. MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. J. Immunol. 160:3056-59
10. + cytotoxic T cell responses to myelin basic protein in multiple sclerosis. J. Immunol. 172:5120-27
11. + T cells in a model for multiple sclerosis. J. Exp. Med. 194:669-76
12. Oldstone MBA. 1989. Molecular mimicry as a mechanism for the cause and as a probe uncovering ellologic agent(s) of autoimmune disease. Curr. Topics Microbiol. Immunol. 145:127-35
13. Wucherpfennig KW, Strominger JL. 1995. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695-705
14. Kozovska M, Zang Y, Aebischer I, et al. 1998. T cell recognition motifs of an immunodominant peptide of myelin basic protein in patients with multiple sclerosis: structural requirements and clinical implications. Eur. J. Immunol. 28:1894-901
15. Hafler DA. 1999. The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis. J. Clin. Invest. 104:527-29
16. Hemmer B, Fleckenstein B, Vergelli M. et al. 1997. Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J. Exp. Med. 185:1651-59
17. Tejada-Simon M, Zang Y, Hong J, et al. 2003. Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann. Neurol. 53:189-97
18. Sriram S, Stratton CW, Yao S, et al. 1999. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann. Neurol. 46:6-14
19. + monocytes in the blood correlates with the presence of active MRI lesions in MS. J. Neuroimmunol. 119:145-49
20. + T cells via CD40 ligand. Proc. Natl. Acad. Sci. USA 94:599-603
21. Genain CP, Nguyen M-H, Letvin NL, et al. 1995. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J. Clin. Invest. 96:2966-74
22. Cross AH, Trotter JL, Lyons J. 2001. B cells and antibodies in CNS demyelinating disease. J. Neuroimmunol. 112:1-14
23. Tejada-Simon M, Hong J, Rivera V, et al. 2002. Skewed autoantibody reactivity to the extracellular domain of myelin oligo-dendrocyte glycoprotein in multiple sclerosis. Immunology 107:403-10
24. Ebers GC, Bulman DE, Sadovnick AD, et al. 1986. A population-based study of multiple sclerosis in twins. N. Engl. J. Med. 315:1638-42
25. Oksenberg JR, Barcellos LF, Hauser SL. 1999. Genetic aspects of multiple sclerosis. Semin. Neurol 19:281-88
26. Andersson PB, Goodkin DE. 1998. Glucocorticosteroid therapy for multiple sclerosis: a critical review. J. Neurol. Sci. 160:16-25
27. Durelli L, Cocito D, Riccio A, et al. 1986. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology 36:238-43
28. Barkhof F, Hommes O, Scheltens P, Valk J. 1991. Quantitative MRI changes in gadolinium-DTPA enhancement after high-dose intravenous methylprednisolone in multiple sclerosis. Neurology 418:1219-22
29. Zivadinov R, Rudick RA, DeMasi R, et al. 2001. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology 57:1239-47
30. Comi G, Filippi M, Wolinsky JS, et al. 2001a. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann. Neurol. 49:290-97
31. Comi G, Filippi M, Wolinsky JS, et al. 2001b. The extension phase of the European-Canadian MRI study demonstrates a sustained effect of glatiramer acetate in patients with relapsing-remitting multiple sclerosis. Neurology 56(Suppl. 3):A255 (Abstr.)
32. IFNB Multiple Sclerosis Study Group. 1993. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:655-61
33. IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. 1995. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 45:1277-85
34. Jacobs LD, Cookfair DL, Rudick RA, et al. 1996. Intramuscular Interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann. Neurol. 39:285-94
35. Paty DW, Li DKB, UBC MS/MRI Study Group, IFNB Multiple Sclerosis Study Group. 1993. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:662-67
36. Simon JH, Jacobs LD, Campion M, et al. 1998. Magnetic resonance studies of intramuscular interferon β-1a for relapsing multiple sclerosis. Ann. Neurol. 43:79-87
37. Li DKB, Paty DW, UBC MS/MRI Analysis Research Group, PRISMS Study Group. 1999. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-β1a in relapsing-remitting multiple sclerosis. Ann. Neurol. 46:197-206
38. PRISMS (Prevention of Relapses and Disability by Interferon-β-1a Subcutaneously in Multiple Sclerosis) Study Group, University of British Columbia MS/MRI Analysis Group. 2001. PRISMS-4: long-term efficacy of interferon-β-1a in relapsing MS. Neurology 56:1628-36
39. Johnson KP, Brooks BR, Cohen JA, et al. 1995. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 45:1268-76
40. Zhang J, Hutton G, Zang Y. 2002a. A comparison of the mechanisms of action of interferon beta and glatiramer acetate in the treatment of multiple sclerosis. Clin. Ther. 24:1998-2021
41. Zang YCQ, Yang D, Hong J, et al. 2000a. Immunoregulation and blocking antibodies induced by interferon beta treatment in MS. Neurology 55:397-404
42. Kozovska ME, Hong J, Zang YCQ, et al. 1999. Interferon beta induces T-helper 2 immune deviation in MS. Neurology 53:1692-97
43. Huang Y-M, Kouwenhoven M, Jin Y-P, et al. 2001. Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression. Mult. Scler. 7:95-99
44. McRae BL, Semnani RT, Hayes MP, et al. 1998. Type I IFNs inhibit human dendritic cell IL-12 production and Th1 cell development. J. Immunol. 160:4298-304
45. Hussein Y, Sanna A, Söderström M, et al. 2001. Glatiramer acetate and IFN-β act on dendritic cells in multiple sclerosis. J. Neuroimmunol. 121:102-10
46. Karp CL, van Boxel-Dezaire AHH, Byrnes AB, et al. 2001. Interferon-β in multiple sclerosis: altering the balance of interleukin-12 and interleukin-10? Curr. Opin. Neurol. 14:361-68
47. Tuohy VK, Yu M, Yin L, et al. 2000. Modulation of the IL-10/IL-12 cytokine circuit by Interferon-β inhibits the development of epitope spreading and disease progression in murine autoimmune encephalomyelitis. J. Neuroimunol. 111:55-63
48. Özenci V, Kouwenhoven M, Huang YM, et al. 1999. Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-β-1b treatment. Scand. J. Immunol. 49:554-61
49. Rep MHG, Schrijver HM, van Lopik T, et al. 1999. Interferon (IFN)-β treatment enhances CD95 and interleukin 10 expression but reduces interferon-γ producing T cells in MS patients. J. Neuroimmunol. 96:92-100
50. Rudick RA, Ransohoff RM, Lee J-C, et al. 1998. In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis. Neurology 50:1294-300
51. Waubant E, Gee L, Bacchetti P, et al. 2001. Relationship between serum levels of IL-10, MRI activity and interferon beta-1a therapy in patients with relapsing remitting MS. J. Neuroimmunol. 112:139-45
52. Liu Z, Pelfry CM, Cotleur A, et al. 2001. Immunomodulatory effects of interferon beta-1a in multiple sclerosis. J. Neuroimmunol. 112:153-62
53. Becher B, Giacomini PS, Pelletier D, et al. 1999. Interferon-γ secretion by peripheral blood-subsets in multiple sclerosis: correlation with disease phase and Interferon-β therapy. Ann. Neurol. 45:247-50
54. Furlan R, Bergami A, Lang R, et al. 2000. Interferon-β treatment in multiple sclerosis patients decreases the number of circulating T cells producing interferon-γ and interleukin-4. J. Neuroimmunol. 111:86-92
55. Wandinger K-P, Strüzebecher C-S, Bielekova B, et al. 2001. Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Ann. Neurol. 50:349-57
56. Racke MK, Martin R, McFarland H, et al. 1992. Copolymer-1-induced inhibition of antigen-specific T cell activation: interference with antigen presentation. J. Neuroimmunol. 37:75-84
57. Teitelbaum D, Milo R, Arnon R, et al. 1992. Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein. Proc. Natl. Acad. Sci. USA 89:137-41
58. Fridkis-Hareli M, Teitelbaum D, Gurevich E, et al. 1994. Direct binding of myelin basic protein and synthetic copolymer 1 to class II major histocompatibility complex molecules on living antigen-presenting cells-specificity and promiscuity. Proc. Natl. Acad. Sci. USA 91:4872-76
59. Ben-Nun A, Mendel I, Bakimer R, et al. 1996. The autoimmune reactivity to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is potentially pathogenic: effect of copolymer 1 on MOG-induced disease. J. Neurol. 243(Suppl. 1):S14-S22
60. Teitelbaum D, Fridkis-Hareli M, Arnon R, et al. 1996. Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses. J. Neuroimmunol. 64:209-17
61. + T cell responses in patients with multiple sclerosis. J. Clin. Invest. 109:641-49
62. Yong VW. 2002. Differential mechanisms of action of interferon-β and glatiramer acetate in MS. Neurology 59:802-8
63. Yu M, Nishiyama A, Trapp BC, et al. 1996. Interferon-β inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. J. Neuroimmunol. 64:91-100
64. Zang Y, Hong J, Robinson R, et al. 2003. Immune regulatory properties and interactions of copolymer-I and beta-interferon 1a in multiple sclerosis. J. Neuroimmunol. 137:144-53
65. Teitelbaum D, Aharoni R, Arnon R, et al. 1988. Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1. Proc. Natl. Acad. Sci. USA 85:9724-28
66. Duda PW, Schmied MC, Cook SL, et al. 2000. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J. Clin. Invest. 105:967-76
67. Lou J, Gasche Y, Zheng L, et al. 1999. Interferon-β inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. Lab. Invest. 79:1015-25
68. Aharoni R, Teitelbaum D, Sela M, et al. 1998. Bystander suppression of experimental autoimmune encephalomyelitis by T cell lines and clones of the Th2 type induced by copolymer 1. J. Neuroimmunol. 91:135-46
69. Aharoni R, Teitelbaum D, Sela M, et al. 1997. Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 94:10821-26
70. Barkhof F. 1999. MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS). Mult. Scler. 5:283-86
71. Fazekas F, Barkhof F, Filippi M, et al. 1999. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology 53:448-56
72. McDonald WI, Compston A, Edan G, et al. 2001. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann. Neurol. 50:121-27
73. Frohman EM, Goodin DS, Calabresi PA, et al. 2003. The utility of MRI in suspected MS. Neurology 61:602-11
74. Miller DH, Barkhof F, Frank JA, et al. 2002a. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 125:1676-95
75. Truyen L, van Waesberghe JHTM, van Walderveen MAA, et al. 1996. Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 47:1469-76
76. Bitsch A, Kuhlmann T, Stadelmann C, et al. 2001. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann. Neurol. 49:793-96
77. Rovaris M, Rocca MA, Filippi M. 2003. Magnetic resonance-based techniques for the study and management of multiple sclerosis. Br. Med. Bull. 65:133-44
78. Miller DH, Thompson AJ, Filippi M. 2003. Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis. J. Neurol. 250:1407-19
79. Zivadinov R, Bakshi R. 2004. Role of MRI in multiple sclerosis I: inflammation and lesions. Front Biosci. 9:665-83
80. Miller DH. 2002. MRI monitoring of MS in clinical trials. Clin. Neurol. Neurosurg. 104:236-43
81. Van Waesberghe JH, van Walderveen MA, Castelijns JA, et al. 1998. Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. Am. J. Neuroradiol. 19:675-83
82. Bagnato F, Jeffreis N, Richert ND, et al. 2003. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 126:1782-89
83. van Walderveen MAA, Kamphorst W, Scheltens P, et al. 1998. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 50:1282-88
84. Zivadinov R, Bakshi R. 2004. Role of MRI in multiple sclerosis II: brain and spinal cord atrophy. Front. Biosci. 9:647-64
85. Bakshi R, Benedict RHB, Bermel RA, et al. 2001. Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings. J. Neuroimaging 11:129-36
86. Bermel RA, Sharma J, Tjoa CW, et al. 2003. A semiautomated measure of whole-brain atrophy in multiple sclerosis. J. Neural. Sci. 208:57-65
87. Filippi M, Tortorella C, Rovaris M, et al. 2000. Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 68:157-61
88. Zivadinov R, Sepcic J, Nasuelli D, et al. 2001. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 70:773-80
89. Bermel RA, Bakshi R, Tjoa C, et al. 2002. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Arch. Neurol. 59:275-80
90. Bakshi R, Czarnecki D, Shaikh ZA, et al. 2000. Brain MRI lesions and atrophy are related to depression in multiple sclerosis. NeuroReport 11:1153-58
91. Dalton CM, Brex PA, Jenkins R, et al. 2002. Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the development of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 73:141-47
92. Filippi M, Rovaris M, Barkhof F, et al. 2001. Brain volume changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis: results from the ETOMS study. J. Neurol. 248(Suppl. 2):113 (Abstr.)
93. Bot JCJ, Barkhof F, Polman CH, et al. 2004. Spinal cord abnormalities in recently diagnosed MS patients; added value of spinal MRI examination. Neurology 62:226-33
94. Tartaglino LM, Friedman DP, Flanders AE, et al. 1995. Multiple sclerosis in the spinal cord: MR appearance and correlation with clinical parameters. Radiology 195:725-32
95. O'Riordan JI, Lossef NA, Phatouros C, et al. 1998. Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination. J. Neurol. Neurosurg. Psychiatry 64:353-57
96. Grossman RI, Barkhof F, Filippi M. 2000. Assessment of spinal cord damage in MS using MRI. J. Neurol. Sci. 172(Suppl. 1): S36-39
97. Lycklama G, Thompson A, Filippi M, et al. 2003. Spinal-cord MRI in multiple sclerosis. Lancet Neurol. 2:555-62
98. Bakshi R, Kinkel PR, Mechtler LL, et al. 1998. Magnetic resonance imaging findings in 22 cases of myelitis: comparison between patients with and without multiple sclerosis. Eur. J. Neurol. 5:35-48
99. Paty DW, Oger JJF, Kastrukoff LF, et al. 1988. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 38:180-85
100. Fazekas F, Offenbacher H, Fuchs S, et al. 1988. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 38:1822-25
101. Barkhof F, Filippi M, Miller DH, et al. 1997. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120:2059-69
102. Tintoré M, Rovira A, Martinez MJ, et al. 2000. Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. Am. J. Neuroradiol. 21:702-6
103. Poser CM, Paty DW, Scheinberg L, et al. 1983. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann. Neurol. 13:227-31
104. Deleted in proof
105. Deleted in proof
106. Deleted in proof
107. Miller DH, Albert PS, Barkhof F, et al. 1996. Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. Ann. Neurol. 39:6-16
108. Filippi M, Dousset V, McFarland HF, et al. 2002. Role of magnetic resonance imaging in the diagnosis and monitoring of multiple sclerosis: consensus report of the White Matter Study Group. J. Magn. Reson. Imaging 15:499-504
109. Miller DH, Khan OA, Sheremata WA, et al. 2003. A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 348:15-23
110. Filippi M, Rocca MA, Martino G, et al. 1998. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann. Neurol. 43:809-14
111. Van Waesberghe JHTM, Kamphorst W, De Groot CJA, et al. 1999. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann. Neurol. 46:747-54
112. Bitsch A, Bruhn H, Vougioukas V, et al. 1999. Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am. J. Neuroradiol. 20:1619-32
113. Fu L, Matthews PM, De Stefano N, et al. 1998. Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121:103-13
114. Goodin DS. 2000. Therapeutic developments in multiple sclerosis. Expert Opin. Invest. Drugs 9:655-70
115. Davidson A, Diamond B. 2001. Autoimmune diseases. N. Engl. J. Med. 345:340-50
116. Wiendl H, Kieseier BC. 2003. Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies. Expert Opin. Invest. Drugs 12:689-712
117. Delves PJ, Roitt IM. 2000. The immune system. Second of two parts. N. Engl. J. Med. 343:108-17
118. Fabry Z, Raine CS, Hart MN. 1994. Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol. Today 15:218-24
119. Cournu-Rebeix I, Genin E, Lesca G, et al. 2003. Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis. Genes Immun. 4:518-23
120. Harlan JM, Winn RK. 2002. Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy. Crit. Care Med. 30:8214-19
121. Tubridy N, Behan PO, Capildeo R, et al. 1999. The effect of anti-α4 integrin anti-body on brain lesion activity in MS. Neurology 53:466-72
122. Frenette PS, Wagner DD. 1996. Adhesion molecules-part I. N. Engl. J. Med. 334:1526-29
123. Frenette PS, Wagner DD. 1996. Adhesion molecules-part II. N. Engl. J. Med. 335:43-45
124. Polman CH, Uitdehaag BMJ. 2003. New and emerging treatment options for multiple sclerosis. Lancet Neurol. 2:563-66
125. Paolillo A, Coles AJ, Molyneux PD, et al. 1999. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 53:751-57
126. Moreau T, Thorpe J, Miller D, et al. 1994. Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 344:298-301
127. Moreau T, Coles A, Wing M, et al. 1996. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 119:225-37
128. Coles AJ, Wing MG, Molyneux P, et al. 1999. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann. Neurol. 46:296-304
129. Coles AJ, Cox A, LePage E. 2003. Campath-1H treatment of multiple sclerosis. Neurology 60 (Suppl. 1):A168-69 (Abstr.)
130. Ben-Nun A, Wekerle H, Cohen IR. 1981. Vaccination against autoimmune encephalomyelitis with T-cell lymphocyte line cells reactive against myelin basic protein. Nature 292:60-61
131. Lider O, Reshef T, Beraud E, et al. 1988. Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science 239:181-84
132. Zhang J, Vandevyver C, Stinissen P, et al. 1995. In vivo clonotypic regulation of human myelin basic protein-reactive T cells by T cell vaccination. J. Immunol. 155:5868-77
133. Zhang J, Medaer R, Stinissen P, et al. 1993. MHC restricted clonotypic depletion of human myelin basic protein-reactive T cells by T cell vaccination. Science 261:1451-54
134. Zang Y, Hong J, Rivera V, et al. 2000b. Preferential recognition of TCR hyper-variable regions by human anti-idiotypic T cells induced by T cell vaccination. J. Immunol. 164:4011-17
135. Hong J, Zang YCQ, Tejada-Simon MV, et al. 2000. Reactivity and regulatory properties of human anti-idiotypic anti-bodies induced by T cell vaccination. J. Immunol. 165:6858-64
136. Zang Y, Hong J, Tejada-Simon M, et al. 2000c. Th2 immune regulation induced by T cell vaccination in patients with multiple sclerosis. Eur. J. Immunol. 30:908-13
137. Hafler D, Cohen IR, Benjamine D, et al. 1992. T cell vaccination in multiple sclerosis: a preliminary report. Clin. Immunol. Immunopathol. 62:307-12
138. Zhang JZ, Rivera VM, Tejada-Simon MV, et al. 2002b. T cell vaccination in multiple sclerosis: results of a preliminary study. J. Neurol. 249:212-18
139. Medaer R, Stinissen P, Truyen L, et al. 1995. Depletion of myelin basic protein autoreactive T cells by T cell vaccination: clinical trial in multiple sclerosis. Lancet 346:807-8
140. Correale J, Lund B, McMillan M, et al. 2000. T cell vaccination in secondary progressive multiple sclerosis. J. Neuroimmunol. 107:130-39
141. Stinissen P, Zhang J, Medaer R, et al. 1996. Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data. J. Neurosci. Res. 45:500-11
142. Zhang J. 2002. T cell vaccination for autoimmune disease: immunologic lesions and clinical experience in multiple sclerosis. Expert Rev. Vaccines 1:285-92
143. Fassas A, Passweg JR, Anagnostopoulos A, et al. 2002. Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J. Neurol. 249:1088-97
144. Sun W, Popat U, Hutton G, et al. 2004. Characteristics of T cell receptor repertoire and myelin-reactive T cells reconstituted from autologous hematopoietic stem cell grafts in multiple sclerosis. Brain 127:996-1008
145. Saiz A, Blanco Y, Carreras E, et al. 2004. Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS. Neurology 62:282-84
146. Youssef S, Stüve O, Patarroyo JC, et al. 2002. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420:78-84
147. Neuhaus O, Strasser-Fuchs S, Fazekas F, et al. 2002. Statins as immunomodulators: comparison with interferon-beta 1b in MS. Neurology 59:990-97
148. Vollmer T, Key L, Durkalski V, et al. 2004. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363:1607-8
149. Confavreux C, Hutchinson M, Hours MM, et al. 1998. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N. Engl. J. Med. 339:285-91
150. Zang YC, Halder JB, Hong J, et al. 2002. Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B. J. Neuroimmunol. 124:106-14
151. Kim S, Liva SM, Dalal MA, et al. 1999. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 52:1230-38
152. Sicotte NL, Liva SM, Klutch R, et al. 2002. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann. Neurol 52:421-28
153. Hong J, Zang YCQ, Hutton G, et al. 2004. Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. J. Neuroimmunol. 152:126-39
154. + T cells in multiple sclerosis: results from an MRI-monitored phase II clinical trial. Ann. Neurol. 51:467-74
155. Morgan EE, Nardo CJ, Diveley JP, et al. 2001. Vaccination with CDR2 BV6S2/6S5 peptide in adjuvant induces peptide-specific T-cell responses in patients with multiple sclerosis. J. Neurosci. Res. 64:298-301
156. Chou YK, Morrison WJ, Weinberg AD, et al. 1994. Immunity to TCR peptides in multiple sclerosis. II. T cell recognition of Vβ5.2 and Vβ6.1 CDR2 peptides. J. Immunol. 152:2520-29
157. Issazadeh S, Zhang M, Sayegh MH, Khoury SJ. 1999. Acquired thymic tolerance: role of CTLA4 in the initiation and maintenance of tolerance in a clinically relevant autoimmune disease model. J. Immunol. 162:761-65
158. Nussenblatt RB, Fortin E, Schiffman R, et al. 1999. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. Proc. Natl. Acad. Sci. USA 96:7462-66
159. Van Der AAA, Hellings N, Medaer R, et al. 2003. T cell vaccination in multiple sclerosis patients with autologous CSF-derived activated T cells: results from a pilot study. Clin. Exp. Immunol. 131:155-68
160. Saleh MN, Gutheil J, Moore M, et al. 2000. A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with refractory immune thrombocytopenia. Semin. Oncol. 27(Suppl. 12):99-103
161. Elices MJ. 2002. BX-471 Berlex. Curr. Opin. Investig. Drugs 3:865-69
162. Brundula V, Rewcastle NB, Metz LM, et al. 2002. Targeting leukocyte MMPs and transmigration. Minocycline as a potential therapy for multiple sclerosis. Brain 125:1297-308
163. Frank JA, Richert N, Lewis B, et al. 2002. A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients. Mult. Scler. 8:24-29
164. Kalkers NF, Barkhof F, Bergers E, et al. 2002. The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult. Scler. 8:532-33