Demographic, Genetic, and Environmental Factors That Modify Disease Course

Neurologic Clinics

Volumn 29, Issue 2, 2011, Pages 323-341

  Marrie, Ruth Ann ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Comorbidity; Genetics; Multiple sclerosis; Prognosis; Race; Smoking; Socioeconomic status

Indexed keywords

HLA ANTIGEN; VITAMIN D;

CLINICAL ASSESSMENT; CLINICAL FEATURE; COMORBIDITY; DEMOGRAPHY; DISABILITY; DISEASE COURSE; ENVIRONMENTAL FACTOR; ETHNICITY; GENETIC ASSOCIATION; HEALTH BEHAVIOR; HEREDITY; HUMAN; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; PROGNOSIS; RACE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SMOKING; SOCIOECONOMICS;

DEMOGRAPHY; DISEASE PROGRESSION; ENVIRONMENT; FEMALE; HEALTH BEHAVIOR; HUMANS; MALE; MULTIPLE SCLEROSIS; PREGNANCY; RISK FACTORS;

EID: 79952848048     PISSN: 07338619     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ncl.2010.12.004     Document Type: Review

References (122)

1. Patzold U., Pocklington P.R. Course of multiple sclerosis. First results of a prospective study carried out of 102 MS patients from 1976-1980. Acta Neurol Scand 1982, 65:248-266.
2. Poser S., Bauer H.J., Poser W. Prognosis of multiple sclerosis. Results from an epidemiological area in Germany. Acta Neurol Scand 1982, 65:347-354.
3. Visscher B.R., Liu K.-S., Clark V.A., et al. Onset symptoms as predictors of mortality and disability in multiple sclerosis. Acta Neurol Scand 1984, 70:321-328.
4. Weinshenker B.G., Bass B., Rice G.P., et al. The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain 1989, 112:1419-1428.
5. Trojano M., Avolio C., Manzari C., et al. Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events. J Neurol Neurosurg Psychiatry 1995, 58:300-306.
6. Confavreux C., Vukusic S., Moreau T., et al. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000, 343:1430-1438.
7. Weinshenker B.G., Rice G.P., Noseworthy J.H., et al. The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain 1991, 114:1045-1056.
8. Runmarker B., Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 1993, 116:117-134.
9. Miller D.H., Hornabrook R.W., Purdie G. The natural history of multiple sclerosis: a regional study with some longitudinal data. J Neurol Neurosurg Psychiatry 1992, 55:341-346.
10. Hammond S.R., McLeod J.G., Macaskill P., et al. Multiple sclerosis in Australia: prognostic factors. J Clin Neurosci 2000, 7:16-19.
11. Tremlett H., Paty D., Devonshire V. Male gender and an older age at onset do not indicate a worse outcome in multiple sclerosis: findings from the natural history of MS in British Columbia, Canada. Mult Scler 2005, 11(Suppl 1):S106.
12. Eriksson M., Andersen O., Runmarker B. Long-term follow-up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler 2003, 9:260-274.
13. Cree B.A., Khan O., Bourdette D., et al. Clinical characteristics of African Americans vs Caucasian Americans with multiple sclerosis. Neurology 2004, 63:2039-2045.
14. Sundstrom P., Nystrom L. Smoking worsens the prognosis in multiple sclerosis. Mult Scler 2008, 14(8):1031-1035.
15. Marrie R.A., Cutter G., Tyry T., et al. Does multiple sclerosis-associated disability differ between races?. Neurology 2006, 66(8):1235-1240.
16. Marrie R.A., Horwitz R.I., Cutter G., et al. Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology 2009, 72(2):117-124.
17. Ebers G., Koopman W.J., Hader W., et al. The natural history of multiple sclerosis: a geographically based study. 8. Familial multiple sclerosis. Brain 2000, 123:641-649.
18. Oturai A.B., Ryder L.P., Fredrikson S., et al. Concordance for disease course and age of onset in Scandinavian multiple sclerosis coaffected sib pairs. Mult Scler 2004, 10:5-8.
19. Hensiek A.E., Seaman S.R., Barcellos L.F., et al. Familial effects on the clinical course of multiple sclerosis. Neurology 2007, 68(5):376-383.
20. Chataway J., Mander A., Robertson N., et al. Multiple sclerosis in sibling pairs: an analysis of 250 families. J Neurol Neurosurg Psychiatry 2001, 71(6):757-761.
21. Weinshenker B.G., Bulman D., Carriere W., et al. A comparison of sporadic and familial multiple sclerosis. Neurology 1990, 40:1354-1358.
22. Robertson N.P., Clayton D., Fraser M., et al. Clinical concordance in sibling pairs with multiple sclerosis. Neurology 1996, 47:347-352.
23. Runmarker B., Martinsson T., Wahlström J., et al. HLA and prognosis in multiple sclerosis. J Neurol 1994, 241(6):385-390.
24. McDonnell G.V., Mawhinney H., Graham C.A., et al. A study of the HLA-DR region in clinical subgroups of multiple sclerosis and its influence on prognosis. J Neurol Sci 1999, 165(1):77-83.
25. Celius E.G., Harbo H.F., Egeland T., et al. Sex and age at diagnosis are correlated with the HLA-DR2, DQ6 haplotype in multiple sclerosis. J Neurol Sci 2000, 178(2):132-135.
26. Mann C.L., Davies M.B., Boggild M.D., et al. Glutathione S-transferase polymorphisms in MS: their relationship to disability. Neurology 2000, 54:552-557.
27. Masterman T., Ligers A., Olsson T., et al. HLA-DR15 is associated with lower age at onset in multiple sclerosis. Ann Neurol 2000, 48:211-219.
28. Fazekas F., Strasser-Fuchs S., Kollegger H., et al. Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis. Neurology 2001, 57:853-857.
29. Weatherby S.J., Thomson W., Pepper L., et al. HLA-DRB1 and disease outcome in multiple sclerosis. J Neurol 2001, 248(4):304-310.
30. Hensiek A.E., Sawcer S.J., Feakes R., et al. HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. J Neurol Neurosurg Psychiatry 2002, 72(2):184-187.
31. Masterman T., Zhang Z., Hellgren D., et al. APOE genotypes and disease severity in multiple sclerosis. Mult Scler 2002, 8:98-103.
32. Villoslada P., Barcellos L.F., Rio J., et al. The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility, clinical course and response to interferon-[beta]. J Neuroimmunol 2002, 130(1/2):194-201.
33. Barcellos L.F., Oksenberg J.R., Begovich A.B., et al. HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 2003, 72(3):710-716.
34. Schreiber K., Otura A.B., Ryder L.P., et al. Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic markers (HLA-DRB1*1501, CCR5 deletion mutation, apolipoprotein E). Mult Scler 2002, 8:295-298.
35. Hensiek A.E., Roxburgh R., Meranian M., et al. Osteopontin gene and clinical severity of multiple sclerosis. J Neurol 2003, 250(8):943-947.
36. Caillier S., Barcellos L.F., Baranzini S.E., et al. Osteopontin polymorphisms and disease course in multiple sclerosis. Genes Immun 2003, 4(4):312-315.
37. Kantor R., Bakhanashvili M., Achiron A. A mutated CCR5 gene may have favorable prognostic implications in MS. Neurology 2003, 61(2):238-240.
38. Gade-Andavolu R., Comings D., MacMurray J., et al. Association of CCR5 [delta]32 deletion with early death in multiple sclerosis. Genet Med 2004, 6(3):126-131.
39. Kantarci O.H., Hebrink D.D., Achenbach S.J., et al. Association of APOE polymorphisms with disease severity in MS is limited to women. Neurology 2004, 62(5):811-814.
40. Partridge J.M., Weatherby S.J., Woolmore J.A., et al. Susceptibility and outcome in MS: associations with polymorphisms in pigmentation-related genes. Neurology 2004, 62(12):2323-2325.
41. Cocco E., Sotgiu A., Costa G., et al. HLA-DR, DQ and APOE genotypes and gender influence in Sardinian primary progressive MS. Neurology 2005, 64(3):564-566.
42. Burwick R.M., Ramsay P.P., Haines J.L., et al. APOE epsilon variation in multiple sclerosis susceptibility and disease severity. Some answers. Neurology 2006, 66:1373-1383.
43. Smestad C., Brynedal B., Jonasdottir G., et al. The impact of HLA-A and -DRB1 on age at onset, disease course and severity in Scandinavian multiple sclerosis patients. Eur J Neurol 2007, 14(8):835-840.
44. Zivadinov R., Uxa L., Bratina A., et al. HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 alleles are associated with more severe disease outcome on MRI in patients with multiple sclerosis International Review of Neurobiology. The neurobiology of multiple sclerosis 2007, Volume 79:521-535. Academic Press. A. Minagar (Ed.).
45. Cournu-Rebeix I., Genin E., Leray E., et al. HLA-DRB1*15 allele influences the later course of relapsing remitting multiple sclerosis. Genes Immun 2008, 9(6):570-574.
46. Sombekke M.H., Lukas C., Crusius J.B.A., et al. HLA-DRB1*1501 and spinal cord magnetic resonance imaging lesions in multiple sclerosis. Arch Neurol 2009, 66(12):1531-1536.
47. Stankovich J., Butzkueven H., Marriott M., et al. HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis. Tissue Antigens 2009, 74(1):17-21.
48. Okuda D.T., Srinivasan R., Oksenberg J.R., et al. Genotype-phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures. Brain 2009, 132(1):250-259.
49. Cree B.A.C., Reich D.E., Khan O., et al. Modification of multiple sclerosis phenotypes by African ancestry at HLA. Arch Neurol 2009, 66(2):226-233.
50. Guerrero A.L., Laherrán E., Gutiérrez F., et al. Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score. Acta Neurol Scand 2008, 117(1):21-25.
51. Silva A.M., Pereira C., Bettencourt A., et al. The role of HLA-DRB1 alleles on susceptibility and outcome of a Portuguese Multiple Sclerosis population. J Neurol Sci 2007, 258(1/2):69-74.
52. Vasconcelos C.C.F., Fernández O., Leyva L., et al. Does the DRB1v1501 allele confer more severe and faster progression in primary progressive multiple sclerosis patients? HLA in primary progressive multiple sclerosis. J Neuroimmunol 2009, 214(1/2):101-103.
53. van Veen T., Crusius J.B., van Winsen L., et al. CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis. J Neuroimmunol 2003, 140(1/2):188-193.
54. DeLuca G.C., Ramagopalan S.V., Herrera B.M., et al. An extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the HLA-DRB1 locus. Proc Natl Acad Sci U S A 2007, 104(52):20896-20901.
55. Ramagopalan S.V., Maugeri N.J., Handunnetthi L., et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 2009, 5(2):e1000369.
56. Pugliatti M., Sotgiu S., Rosati G. The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 2002, 104:182-191.
57. Noonan C.W., Williamson D.M., Henry J.P., et al. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis 2010, 7(1):A12.
58. Svenson L.W., Warren S., Warren K.G., et al. Prevalence of multiple sclerosis in First Nations people of Alberta. Can J Neurol Sci 2007, 34:175-180.
59. Modi G., Mochan A., Modi M., et al. Demyelinating disorder of the central nervous system occurring in black South Africans. J Neurol Neurosurg Psychiatry 2001, 70:500-505.
60. Mirsattari S.M., Johnston J.B., McKenna R., et al. Aboriginals with multiple sclerosis: HLA types and predominance of neuromyelitis optica. Neurology 2001, 56:317-323.
61. Wingerchuk D.M., Lennon V.A., Pittock S.J., et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006, 66:1485-1489.
62. Lennon V.A., Wingerchuk D.M., Kryzer T.J., et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004, 364:2106-2112.
63. Kira J. Neuromyelitis optica and Asian phenotype of multiple sclerosis. Ann N Y Acad Sci 2008, 1142:58-71. The Year in Neurology 2008.
64. Naismith R.T., Trinkaus K., Cross A.H. Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Mult Scler 2006, 12(6):775-781.
65. Cree B.A., Al-Sabbagh A., Bennett R., et al. Response to interferon beta-1a treatment in African American multiple sclerosis patients. Arch Neurol 2005, 62:1681-1683.
66. Weinstock-Guttman B., Jacobs L.D., Brownscheidle C.M., et al. Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium. Mult Scler 2003, 9:293-298.
67. Phillips P.H., Newman N.J., Lynn M.J. Optic neuritis in African Americans. Arch Neurol 1998, 55:186-192.
68. Mowry E.M., Pesic M., Grimes B., et al. Clinical predictors of early second event in patients with clinically isolated syndrome. J Neurol 2009, 256(7):1061-1066.
69. Kaufman M.D., Johnson S.K., Moyer D., et al. Multiple sclerosis: severity and progression rate in African Americans compared with whites. Am J Phys Med Rehabil 2003, 82:582-590.
70. Wallin M.T., Page W.F., Kurtzke J.F. Epidemiology of multiple sclerosis in US veterans. VIII. Long-term survival after onset of multiple sclerosis. Brain 2000, 123:1677-1687.
71. Boster A.L., Endress C.F., Hreha S.A., et al. Pediatric-onset multiple sclerosis in African-American Black and European-Origin white patients. Pediatr Neurol 2009, 40(1):31-33.
72. Rinker J.R., Trinkaus K., Naismith R.T., et al. Higher IgG index found in African Americans versus Caucasians with multiple sclerosis. Neurology 2007, 69(1):68-72.
73. Schwid S.R., Thorpe J., Sharief M., et al. Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE study. Arch Neurol 2005, 62(5):785-792.
74. A dictionary of epidemiology 1988, 44. Oxford University Press, New York. 2nd edition. J.M. Last (Ed.).
75. Bamshad M. Genetic influences on health: does race matter?. JAMA 2005, 294(8):937-946.
76. Last J.M. Social and behavioral determinants of health. Public health and human ecology 1987, 211-242. Appleton & Lange, East Norwalk (CT). J.M. Last (Ed.).
77. Braveman P.A., Cubbin C., Egerter S., et al. Socioeconomic status in health research: one size does not fit all. JAMA 2005, 294:2879-2888.
78. Kaplan G.A., Keil J.E. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation 1993, 88:1973-1998.
79. Steenland K., Hu S., Walker J. All-cause and cause-specific mortality by socioeconomic status among employed persons in 27 US states, 1984-1997. Am J Public Health 2004, 94:1037-1042.
80. Stephansson O., Dickman P.W., Johansson A.L.V., et al. The influence of socioeconomic status on stillbirth risk in Sweden. Int J Epidemiol 2001, 30:1296-1301.
81. Minkler M., Fuller-Thomson E., Guralnik J.M. Gradient of disability across the socioeconomic spectrum in the United States. N Engl J Med 2006, 355:695-703.
82. Marrie R.A., Horwitz R., Cutter G., et al. Comorbidity, socioeconomic status, and multiple sclerosis. Mult Scler 2008, 14(8):1091-1098.
83. Shabas D., Heffner M. Multiple sclerosis management for low-income minorities. Mult Scler 2005, 11:635-640.
84. Minden S.L., Hoaglin D.C., Hadden L., et al. Access to and utilization of neurologists by people with multiple sclerosis. Neurology 2008, 70(13_Part_2):1141-1149.
85. Beatty P.W., Hagglund K.J., Neri M.T., et al. Access to health care services among people with chronic or disabling conditions: patterns and predictors. Arch Phys Med Rehabil 2003, 84:1417-1425.
86. Hellwig K., Brune N., Haghikia A., et al. Reproductive counselling, treatment and course of pregnancy in 73 German MS patients. Acta Neurol Scand 2008, 118(1):24-28.
87. Confavreux C., Hutchinson M., Hours M.M., et al. Pregnancy in Multiple Sclerosis Group. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med 1998, 339:285-291.
88. Poser S., Poser W. Multiple sclerosis and gestation. Neurology 1983, 33(11):1422-1427.
89. Weinshenker B.G., Hader W., Carriere W., et al. The influence of pregnancy on disability from multiple sclerosis: a population-based study in Middlesex County, Ontario. Neurology 1989, 39(11):1438-1440.
90. Runmarker B., Andersen O. Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain 1995, 118(1):253-261.
91. Thompson D.S., Nelson L.M., Burns A., et al. The effects of pregnancy in multiple sclerosis: a retrospective study. Neurology 1986, 36(8):1097-1099.
92. Tremlett H., Yousefi M., Devonshire V., et al. Impact of multiple sclerosis relapses on progression diminishes with time. Neurology 2009, 73(20):1616-1623.
93. D'Hooghe M.B., Nagels G., Uitdehaag B.M.J. Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry 2010, 81(1):38-41.
94. Gijsen R., Hoeymans N., Schellevis F.G., et al. Causes and consequences of comorbidity: a review. J Clin Epidemiol 2001, 54:661-674.
95. Sprangers M.A.G., de Regt E.B., Andries F., et al. Which chronic conditions are associated with better or poorer quality of life?. J Clin Epidemiol 2000, 53:895-907.
96. Battafarano R.J., Piccirillo J.F., Meyers B.F., et al. Impact of comorbidity on survival after surgical resection in patients with stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 2006, 123:280-287.
97. Braunstein J.B., Anderson G.F., Gerstenblith G., et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure. J Am Coll Cardiol 2003, 42:1226-1233.
98. Greenfield S., Apolone G., McNeil B.J., et al. The importance of co-existent disease in the occurrence of postoperative complications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip replacement. Med Care 1993, 31:141-154.
99. Tourbah A., Clapin A., Gout O., et al. Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study. Arch Neurol 1998, 55:517-521.
100. Hohol M.J., Orav E.J., Weiner H.L. Disease Steps in multiple sclerosis: a simple approach to evaluate disease progression. Neurology 1995, 45:251-255.
101. Kirby S., Brown M.G., Murray T.J., et al. Progression of multiple sclerosis in patients with other autoimmune diseases. Mult Scler 2005, 11(Suppl 1):S28-S29.
102. Kirby S., Fisk J.D., Brown M.G., et al. Progression of multiple sclerosis in patients with psychiatric syndromes. Mult Scler 2005, 11(Suppl 1):S28-S29.
103. Dallmeijer A.J., Beckerman H., Groot V.D., et al. Long-term effect of comorbidity on the course of physical functioning in patients after stroke and with multiple sclerosis. J Rehabil Med 2009, 41(5):322-326.
104. Marrie R.A., Rudick R., Horwitz R., et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 2010, 74:1041-1047.
105. National Center for Health Statistics.Health, United States, 2005 With chartbook on trends in the health of Americans 2005, U.S. Department of Health and Human Services, Hyattsville (MD).
106. Tammemagi C.M., Neslund-Dudas C., Simoff M., et al. Smoking and lung cancer survival. The role of comorbidity and treatment. Chest 2004, 125:27-37.
107. Hernan M.A., Jick S.S., Logroscino G., et al. Cigarette smoking and the progression of multiple sclerosis. Brain 2005, 128(Pt 6):1461-1465.
108. Pittas F., Ponsonby A.L., van der Mei I.A., et al. Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis. J Neurol 2009, 256(4):577-585.
109. Koch M., van Harten A., Uyttenboogaart M., et al. Cigarette smoking and progression in multiple sclerosis. Neurology 2007, 69(15):1515-1520.
110. D'Hooghe M.B., Nagels G. Smoking behavior and multiple sclerosis severity. Mult Scler 2005, 11(Suppl 1):S27.
111. Healy B.C., Ali E.N., Guttmann C.R.G., et al. Smoking and disease progression in multiple sclerosis. Arch Neurol 2009, 66(7):858-864.
112. Zivadinov R., Weinstock-Guttman B., Hashmi K., et al. Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis. Neurology 2009, 73(7):504-510.
113. Sena A., Couderc R., Ferret-Sena V., et al. Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis. Eur J Neurol 2009, 16(7):832-837.
114. Di Pauli F., Reindl M., Ehling R., et al. Smoking is a risk factor for early conversion to clinically definite multiple sclerosis. Mult Scler 2008, 14(8):1026-1030.
115. Munger K.L., Chitnis T., Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology 2009, 73(19):1543-1550.
116. Cantorna M.T. Vitamin D and multiple sclerosis: an update. Nutr Rev 2008, 66(s2):S135-S138.
117. Tremlett H., van der Mei I.A., Pittas F., et al. Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 2008, 31(4):271-279.
118. Soilu-Hanninen M., Laaksonen M., Laitinen I., et al. A longitudinal study of serum 25-hydroxyvitamin D and intact PTH levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 2008, 79:152-157.
119. Mowry E.M., Krupp L.B., Milazzo M., et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 2010, 67(5):618-624.
120. Weinshenker B.G., Wingerchuk D.M., Liu Q., et al. Genetic variation in the tumor necrosis factor alpha gene and the outcome of multiple sclerosis. Neurology 1997, 49(2):378-385.
121. Weinshenker B.G., Santrach P., Bissonet A.S., et al. Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study. Neurology 1998, 51(3):742-747.
122. van Veen T., Nielsen J., Berkhof J., et al. CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis. J Neuroimmunol 2007, 190(1/2):157-164.