Evolving expectations around early management of multiple sclerosis

Therapeutic Advances in Neurological Disorders

Volumn 3, Issue 6, 2010, Pages 351-367

  Gold, Ralf ^a   Wolinsky, Jerry S ^b   Amato, Maria Pia ^c   Comi, Giancarlo ^d  

^a ST JOSEF HOSPITAL   (Germany)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF FLORENCE   (Italy)

^d SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

clinically isolated syndrome; cognition; disease modifying treatments early treatment; interferon beta; multiple sclerosis

Indexed keywords

BETA INTERFERON; BETA1A INTERFERON; BRAIN DERIVED NEUROTROPHIC FACTOR; CREATINE; GAMMA INTERFERON; GLATIRAMER; GLUTAMIC ACID; IBUPROFEN; IMMUNOMODULATING AGENT; INTERFERON BETA SERINE; MATRIX METALLOPROTEINASE; N ACETYLASPARTIC ACID; NERVE GROWTH FACTOR; PARACETAMOL; PLACEBO; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA;

ALLERGIC ENCEPHALOMYELITIS; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; AXONAL INJURY; BIOACCUMULATION; BRAIN ATROPHY; CEREBROSPINAL FLUID ANALYSIS; CLINICAL TRIAL; COGNITION; COGNITIVE DEFECT; COST UTILITY ANALYSIS; CYTOKINE PRODUCTION; DEMYELINATING DISEASE; DIFFUSION TENSOR IMAGING; DISEASE COURSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; EARLY DIAGNOSIS; EARLY INTERVENTION; ENCEPHALITIS; ENVIRONMENTAL FACTOR; EXPECTATION; FLU LIKE SYNDROME; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENETIC RISK; HIGH RISK PATIENT; HUMAN; IMMUNOMODULATION; IMMUNOPATHOGENESIS; INJECTION SITE REACTION; MULTIPLE SCLEROSIS; MYELITIS; NERVE INJURY; NEUROPATHOLOGY; NEUROPROTECTION; NUCLEAR MAGNETIC RESONANCE IMAGING; OPTIC NEURITIS; PERIPHERAL BLOOD MONONUCLEAR CELL; PHYSICAL DISABILITY; PRIORITY JOURNAL; PROGNOSIS; QUALITY OF LIFE; RELAPSE; REMISSION; REVIEW; SINGLE DRUG DOSE;

EID: 78649926600     PISSN: 17562856     EISSN: None     Source Type: Journal    
DOI: 10.1177/1756285610385608     Document Type: Review

References (109)

1. Achiron, A. ( 2004) Predicting the course of relapsing-remitting MS using longitudinal disability curves. J Neurol 251(Suppl. 5): v65-v68.
2. Amato, M.P., Bartolozzi, M.L., Zipoli, V., Portaccio, E., Mortilla, M., Guidi, L. et al. (2004) Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 63: 89-93.
3. Amato, M.P., Ponziani, G., Pracucci, G., Bracco, L., Siracusa, G. and Amaducci, L. ( 1995) Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up. Arch Neurol 52: 168-172.
4. Amato, M.P., Ponziani, G., Siracusa, G. and Sorbi, S. ( 2001) Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol 58: 1602-1606.
5. Amato, M.P., Portaccio, E., Stromillo, M.L., Goretti, B., Zipoli, V., Siracusa, G. et al. (2008) Cognitive assessment and quantitative magnetic resonance metrics can help to identify benign multiple sclerosis. Neurology 71: 632-638.
6. Amato, M.P., Zipoli, V., Goretti, B., Portaccio, E., de Caro, M.F., Ricchiuti, L. et al. (2006 a) Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 253: 1054-1059.
7. Amato, M.P., Zipoli, V. and Portaccio, E. ( 2006b) Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci 245: 41-46.
8. Anderson, V.M., Fernando, K.T., Davies, G.R., Rashid, W., Frost, C., Fox, N.C. et al. (2007) Cerebral atrophy measurement in clinically isolated syndromes and relapsing remitting multiple sclerosis: a comparison of registration-based methods. J Neuroimaging 17: 61-68.
9. Andersson, P.B., Waubant, E., Gee, L. and Goodkin, D.E. ( 1999) Multiple sclerosis that is progressive from the time of onset: clinical characteristics and progression of disability. Arch Neurol 56: 1138-1142.
10. Audoin, B., Ibarrola, D., Ranjeva, J.P., Confort-Gouny, S., Malikova, I., Ali-Cherif, A. et al. (2003) Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp 20: 51-58.
11. Azoulay, D., Mausner-Fainberg, K., Urshansky, N., Fahoum, F. and Karni, A. (2009) Interferon-beta therapy up-regulates BDNF secretion from PBMCs of MS patients through a CD40-dependent mechanism. J Neuroimmunol 211: 114-119.
12. Barkhof, F., Calabresi, P.A., Miller, D.H. and Reingold, S.C. (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5: 256-266.
13. Barkhof, F., Filippi, M., Miller, D.H., Scheltens, P., Campi, A., Polman, C.H. et al. (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120: 2059-2069.
14. Barkhof, F., van Waesberghe, J.H., Filippi, M., Yousry, T., Miller, D.H., Hahn, D. et al. (2001) T (1) hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment. Brain 124: 1396-1402.
15. Beatty, W.W., Blanco, C.R., Wilbanks, S.L., Paul, R.H. and Hames, K.A. ( 1995a) Demographic, clinical, and cognitive characteristics of multiple sclerosis patients who continue to work. Neurorehabil Neural Repair 9: 167-173.
16. Beatty, W.W., Goodkin, D.E., Hertsgaard, D. and Monson, N. ( 1990) Clinical and demographic predictors of cognitive performance in multiple sclerosis Do diagnostic type, disease duration, and disability matter? Arch Neurol 47: 305-308.
17. Beatty, W.W., Paul, R.H., Wilbanks, S.L., Hames, K.A., Blanco, C.R. and Goodkin, D.E. ( 1995b) Identifying multiple sclerosis patients with mild or global cognitive impairment using the Screening Examination for Cognitive Impairment (SEFCI). Neurology 45: 718-723.
18. Benedict, R.H., Cookfair, D., Gavett, R., Gunther, M., Munschauer, F., Garg, N. et al. (2006) Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc 12: 549-558.
19. Biernacki, K., Antel, J.P., Blain, M., Narayanan, S., Arnold, D.L. and Prat, A. ( 2005) Interferon beta promotes nerve growth factor secretion early in the course of multiple sclerosis. Arch Neurol 62: 563-568.
20. Brex, P.A., Ciccarelli, O., O'Riordan, J.I., Sailer, M., Thompson, A.J. and Miller, D.H. ( 2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346: 158-164.
21. Cadavid, D., Cheriyan, J., Skurnick, J., Lincoln, J.A., Wolansky, L.J. and Cook, S.D. (2009) New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate. J Neurol Neurosurg Psychiatry 80: 1337-1343.
22. Chiaravalloti, N.D. and de Luca, J. ( 2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7: 1139-1151.
23. Clerico, M., Faggiano, F., Palace, J., Rice, G., Tintore, M. and Durelli, L. ( 2008) Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Database Syst Rev 2: CD005278.
24. Comi, G. ( 2009) Shifting the paradigm toward earlier treatment of multiple sclerosis with interferon beta. Clin Ther 31: 1142-1157.
25. Comi, G., Filippi, M. and Barkhof, F. ( 2002) Effect of early Interferon treatment on conversion to definite multiple sclerosis: The ETOMS study 4-year results. Mult Scler 8(Suppl. 1): S23.
26. Comi, G., Filippi, M., Barkhof, F., Durelli, L., Edan, G., Fernandez, O. et al. (2001 a) Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357: 1576-1582.
27. Comi, G., Filippi, M. and Wolinsky, J.S. ( 2001b) 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. European / Canadian Glatiramer Acetate Study Group. Ann Neurol 49: 290-297.
28. Comi, G., Martinelli, V., Rodegher, M., Moiola, L., Bajenaru, O., Carra, A. et al. (2009) Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 374: 1503-1511.
29. Croze, E., Beekman, J., Knappertz, V., Sandbrink, R., Pohl, C., Paz, P. et al. (2009 a) Betaseron increases expression of metallothioneins in relapsing-remitting multiple sclerosis patients suggesting a role for betaferon in neuroprotection. 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS), Duesseldorf, Abstract P 476.
30. Croze, E., Velichko, S., Tran, T., Yamaguchi, K., Salamon, H., Reder, A. et al. (2009 b) Betaseron induces a novel alternate start transcript in cells obtained from relapsing-remitting multiple sclerosis patients and human brain that is associated with control of oxidative resistance. 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS), Duesseldorf, Abstract P 475.
31. Dalton, C.M., Brex, P.A., Miszkiel, K.A., Hickman, S.J., MacManus, D.G., Plant, G.T. et al. (2002) Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 52: 47-53.
32. de Stefano, N., Narayanan, S., Francis, G.S., Arnaoutelis, R., Tartaglia, M.C., Antel, J.P. et al. (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58: 65-70.
33. Durand, M., Kolpak, A., Farrell, T., Elliott, N.A., Shao, W., Brown, M. et al. (2007) The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins. BMC Cell Biol 8: 13.
34. Ebers, G. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. ( 1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing / remitting multiple sclerosis. Lancet 352: 1498-1504.
35. Flachenecker, P. and Stuke, K. ( 2008) National MS registries. J Neurol 255(Suppl. 6): 102-108.
36. Frohman, E.M., Racke, M.K. and Raine, C.S. ( 2006) Multiple sclerosis-the plaque and its pathogenesis. N Engl J Med 354: 942-955.
37. Giacomini, P.S. and Arnold, D.L. ( 2008) Non-conventional MRI techniques for measuring neuroprotection, repair and plasticity in multiple sclerosis. Curr Opin Neurol 21: 272-277.
38. Glanz, B.I., Holland, C.M., Gauthier, S.A., Amunwa, E.L., Liptak, Z., Houtchens, M.K. et al. (2007) Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis. Mult Scler 13: 1004-1010.
39. Gonsette, R.E. ( 2008) Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J Neurol Sci 274: 48-53.
40. Hafler, D.A., Slavik, J.M., Anderson, D.E., O'Connor, K.C., de Jager, P. and Baecher-Allan, C. ( 2005) Multiple sclerosis. Immunol Rev 204: 208-231.
41. Hasan, K.M., Gupta, R.K., Santos, R.M., Wolinsky, J.S. and Narayana, P.A. ( 2005) Diffusion tensor fractional anisotropy of the normal-appearing seven segments of the corpus callosum in healthy adults and relapsing-remitting multiple sclerosis patients. J Magn Reson Imaging 21: 735-743.
42. Hwang, Y.P., Kim, H.G., Han, E.H. and Jeong, H.G. ( 2008) Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner. Toxicol Appl Pharmacol 231: 318-327.
43. Jacobs, L.D., Beck, R.W., Simon, J.H., Kinkel, R.P., Brownscheidle, C.M., Murray, T.J. et al. (2000) Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343: 898-904.
44. Kappos, L., Freedman, M.S., Polman, C.H., Edan, G., Hartung, H.P., Miller, D.H. et al. (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370: 389-397.
45. Kappos, L., Freedman, M.S., Polman, C.H., Edan, G., Hartung, H.P., Miller, D.H. et al. (2009) Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 8: 987-997.
46. Kappos, L., Polman, C.H., Freedman, M.S., Edan, G., Hartung, H.P., Miller, D.H. et al. (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67: 1242-1249.
47. Kinkel, R.P., Kollman, C., O'Connor, P., Murray, T.J., Simon, J., Arnold, D. et al. (2006) IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 66: 678-684.
48. Kinkel, R.P., Tanner, J.P., Simon, J., O'Connor, P.W., Kollman, C. and CHAMPION Study Group. (2009) CHAMPIONS extension study: 10 year follow-up after a clinically isolated syndrome (CIS) in high risk patients. Neurology 72(Suppl): A315; Poster 306.137.
49. Kovarik, P., Sauer, I. and Schaljo, B. ( 2007) Molecular mechanisms of the anti-inflammatory functions of interferons. Immunobiology 212: 895-901.
50. Kuhlmann, T., Lingfeld, G., Bitsch, A., Schuchardt, J. and Bruck, W. ( 2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125: 2202-2212.
51. Langdon, D., Benedict, R., Wicklein, E.M. and Fredrikson, S. ( 2009a) Report of cognitive difficulties by clinically isolated syndrome patients and carers: the multiple sclerosis neuropsychological questionnaire data from the CogniCIS baseline cohort. 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS), Duesseldorf, Abstract P406.
52. Langdon, D., Benedict, R., Wicklein, E.M. and Fredrikson, S. ( 2009b) Report of cognitive difficulties by multiple sclerosis patients and carers: the Multiple Sclerosis Neuropsychological Questionnaire data from the CogniMS Baseline Cohort. 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS), Duesseldorf, Abstract P407.
53. Lassmann, H., Bruck, W. and Lucchinetti, C.F. ( 2007) The immunopathology of multiple sclerosis: an overview. Brain Pathol 17: 210-218.
54. Lazzaro, C., Bianchi, C., Peracino, L., Zacchetti, P. and Uccelli, A. (2009) Economic evaluation of treating clinically isolated syndrome and subsequent multiple sclerosis with interferon beta-1b. Neurol Sci 30: 21-31.
55. Lebrun, C., Bensa, C., Debouverie, M., de Seze, J., Wiertlievski, S., Brochet, B. et al. (2008) Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile. J Neurol Neurosurg Psychiatry 79: 195-198.
56. Li, D.K., Zhao, G.J. and Paty, D.W. ( 2001) Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology 56: 1505-1513.
57. Linker, R.A., Lee, D.-H., Demir, S., Wiese, S., Kruse, N., Siglienti, I. et al. (2010) Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 133: 2248-2263.
58. Lopez-Diego, R.S. and Weiner, H.L. ( 2008) Novel therapeutic strategies for multiple sclerosis-a multifaceted adversary. Nat Rev Drug Discov 7: 909-925.
59. Lublin, F.D. and Reingold, S.C. ( 1996) Defining the clinical course of multiple sclerosis: results of an international survey National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46: 907-911.
60. Lynch, S.G., Parmenter, B.A. and Denney, D.R. ( 2005) The association between cognitive impairment and physical disability in multiple sclerosis. Mult Scler 11: 469-476.
61. McDonald, W.I., Compston, A., Edan, G., Goodkin, D., Hartung, H.P., Lublin, F.D. et al. (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50: 121-127.
62. McIntosh-Michaelis, S.A., Roberts, M.H., Wilkinson, S.M., Diamond, I.D., McLellan, D.L., Martin, J.P. et al. (1991) The prevalence of cognitive impairment in a community survey of multiple sclerosis. Br J Clin Psychol 30: 333-348.
63. McMahon, E.J., Bailey, S.L., Castenada, C.V., Waldner, H. and Miller, S.D. ( 2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 11: 335-339.
64. Miller, D., Barkhof, F., Montalban, X., Thompson, A. and Filippi, M. ( 2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 4: 281-288.
65. Miller, D.H. ( 2004) Biomarkers and surrogate outcomes in neurodegenerative disease: lessons from multiple sclerosis. NeuroRx 1: 284-294.
66. Minagar, A. and Alexander, J.S. ( 2003) Blood-brain barrier disruption in multiple sclerosis. Mult Scler 9: 540-549.
67. Montalban, X., Tintore, M., Swanton, J., Barkhof, F., Fazekas, F., Filippi, M. et al. (2010) MRI criteria for MS in patients with clinically isolated syndromes. Neurology 74: 427-434.
68. Morrissey, S.P., Miller, D.H., Kendall, B.E., Kingsley, D.P., Kelly, M.A., Francis, D.A. et al. (1993) The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study. Brain 116: 135-146.
69. Munz, C., Lunemann, J.D., Getts, M.T. and Miller, S.D. (2009) Antiviral immune responses: triggers of or triggered by autoimmunity ? Nat Rev Immunol 9: 246-258.
70. Narayanan, S., de Stefano, N., Francis, G.S., Arnaoutelis, R., Caramanos, Z., Collins, D.L. et al. (2001) Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 248: 979-986.
71. National Clinical Advisory Board (2008) Disease Management Consensus Statement. National Multiple Sclerosis Society Available at: http://www.nationalmssociety.org/for-professionals/healthcare-professionals/publications/expert-opinion-papers/index.aspx.
72. Neuhaus, O., Farina, C., Yassouridis, A., Wiendl, H., Then Bergh, F., Dose, T. et al. (2000) Multiple sclerosis: comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. Proc Natl Acad Sci U S A 97: 7452-7457.
73. Noseworthy, J.H., Lucchinetti, C., Rodriguez, M. and Weinshenker, B.G. ( 2000) Multiple sclerosis. N Engl J Med 343: 938-952.
74. O'Connor, P., Filippi, M., Arnason, B., Comi, G., Cook, S., Goodin, D. et al. (2009) 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol 8: 889-897.
75. Optic Neuritis Study Group (2004) Long-term brain magnetic resonance imaging changes after optic neuritis in patients without clinically definite multiple sclerosis. Arch Neurol 61: 1538-1541.
76. Ormerod, I.E., Miller, D.H., McDonald, W.I., du Boulay, E.P., Rudge, P., Kendall, B.E. et al. (1987) The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain 110: 1579-1616.
77. Panitch, H., Goodin, D.S., Francis, G., Chang, P., Coyle, P.K., O'Connor, P. et al. (2002) Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology 59: 1496-1506.
78. Peterson, J.W., Bo, L., Mork, S., Chang, A. and Trapp, B.D. ( 2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50: 389-400.
79. Peterson, J.W. and Trapp, B.D. ( 2005) Neuropathobiology of multiple sclerosis. Neurol Clin 23: 107-129,, vi-vii.
80. Pittock, S.J. ( 2009) Uncertain BENEFIT of early interferon beta-1b treatment. Lancet Neurol 8: 970-971.
81. Polman, C.H., Reingold, S.C., Edan, G., Filippi, M., Hartung, H.P., Kappos, L. et al. (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58: 840-846.
82. Portaccio, E., Zipoli, V., Goretti, B., de Stefano, N. and Amato, M.P. ( 2009) Evidence for relative cortical sparing in benign multiple sclerosis: a longitudinal magnetic resonance imaging study. Mult Scler 15, 403; author reply 404.
83. Poser, C.M., Paty, D.W., Scheinberg, L., McDonald, W.I., Davis, F.A., Ebers, G.C. et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13: 227-231.
84. Potagas, C., Giogkaraki, E., Koutsis, G., Mandellos, D., Tsirempolou, E., Sfagos, C. et al. (2008) Cognitive impairment in different MS subtypes and clinically isolated syndromes. J Neurol Sci 267: 100-106.
85. Pozzilli, C., Miltenburger, C., Guenther, O., Bugge, J. and Ecari, U. ( 2009) Elements of a patient support programme influencing quality of life in patients with MS: one-year results from an international, observational study. J Neurol 256(Suppl. 2): P465.
86. Prinz, M., Schmidt, H., Mildner, A., Knobeloch, K.P., Hanisch, U.K., Raasch, J. et al. (2008) Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 28: 675-686.
87. Rao, S.M., Leo, G.J., Bernardin, L. and Unverzagt, F. ( 1991a) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41: 685-691.
88. Rao, S.M., Leo, G.J., Ellington, L., Nauertz, T., Bernardin, L. and Unverzagt, F. ( 1991b) Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 41: 692-696.
89. Rao, S.M., Reingold, S.C., Ron, M.A., Lyon-Caen, O. and Comi, G. ( 1993) Workshop on Neurobehavioral Disorders in Multiple Sclerosis. Diagnosis, underlying disease, natural history, and therapeutic intervention, Bergamo, Italy, June 25-27, 1992. Arch Neurol 50: 658-662.
90. Reder, A.T., Velichko, S., Yamaguchi, K.D., Hamamcioglu, K., Ku, K., Beekman, J. et al. (2008) IFN-beta1b induces transient and variable gene expression in relapsing-remitting multiple sclerosis patients independent of neutralizing antibodies or changes in IFN receptor RNA expression. J Interferon Cytokine Res 28: 317-331.
91. Rovaris, M., Riccitelli, G., Judica, E., Possa, F., Caputo, D., Ghezzi, A. et al. (2008) Cognitive impairment and structural brain damage in benign multiple sclerosis. Neurology 71: 1521-1526.
92. Rudick, R.A., Fisher, E., Lee, J.C., Simon, J. and Jacobs, L. ( 1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53: 1698-1704.
93. Schwid, S.R. and Bever, C.T.J. ( 2001) The cost of delaying treatment in multiple sclerosis: What is lost is not regained. Neurology 56: 1620.
94. Shao, W., Halachmi, S. and Brown, M. ( 2002) ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol 22: 3358-3372.
95. Soderstrom, M., Ya-Ping, J., Hillert, J. and Link, H. ( 1998) Optic neuritis: prognosis for multiple sclerosis from MRI, CSF, and HLA findings. Neurology 50: 708-714.
96. Stadelmann, C., Kerschensteiner, M., Misgeld, T., Bruck, W., Hohlfeld, R. and Lassmann, H. ( 2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125: 75-85.
97. Tao, G., Datta, S., He, R., Nelson, F., Wolinsky, J.S. and Narayana, P.A. (2009) Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry. J Neurol Sci 282: 39-46.
98. Tintore, M., Rovira, A., Rio, J., Nos, C., Grive, E., Tellez, N. et al. (2006) Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 67: 968-972.
99. Tintore, M., Rovira, A., Rio, J., Tur, C., Pelayo, R., Nos, C. et al. (2008) Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology 70: 1079-1083.
100. Trapp, B.D., Peterson, J., Ransohoff, R.M., Rudick, R., Mork, S. and Bo, L. ( 1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338: 278-285.
101. Trapp, B.D. and Stys, P.K. (2009) Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol 8: 280-291.
102. Trojano, M., Paolicelli, D., Bellacosa, A. and Cataldo, S. ( 2003) The transition from relapsing-remitting MS to irreversible disability: clinical evaluation. Neurol Sci 24(Suppl. 5): S268-S270.
103. Trojano, M., Pellegrini, F., Fuiani, A., Paolicelli, D., Zipoli, V., Zimatore, G.B. et al. (2007) New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol 61: 300-306.
104. Trojano, M., Pellegrini, F., Paolicelli, D., Fuiani, A., Zimatore, G.B., Tortorella, C. et al. (2009) Real-life impact of early interferonbeta therapy in relapsing multiple sclerosis. Ann Neurol 66: 513-520.
105. van Waesberghe, J.H., Kamphorst, W., de Groot, C.J., van Walderveen, M.A., Castelijns, J.A., Ravid, R. et al. (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46: 747-754.
106. Weinshenker, B.G., Gilbert, J.J. and Ebers, G.C. ( 1990) Some clinical and pathologic observations on chronic myelopathy: a variant of multiple sclerosis. J Neurol Neurosurg Psychiatry 53: 146-149.
107. Zipoli, V., Goretti, B., Hakiki, B., Siracusa, G., Sorbi, S., Portaccio, E. et al. (2010) Cognitive impairment predicts conversion to multiple sclerosis in clinically isolated syndromes. Mult Scler 16: 62-67.
108. Zivadinov, R., Munschauer, F.E., Ramanathan, M., Benedict, R.H. and Weinstock-Guttman, B. ( 2008a) Clinical efficacy, effects on MRI and tolerability of weekly intramuscular interferon-beta-1a in patients with MS and CIS. Drugs Today (Barc) 44: 601-613.
109. Zivadinov, R., Stosic, M., Cox, J.L., Ramasamy, D.P. and Dwyer, M.G. ( 2008b) The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome. J Neurol 255(Suppl. 1): 61-74.