Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pathogenesis and epidemiology of multiple sclerosis

Michael J Olek, DO
Ellen Mowry, MD, MCR
Section Editor
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD


Diseases that affect central nervous system myelin can be categorized as demyelinating (acquired, usually inflammatory) and dysmyelinating (abnormal formation of myelin, usually due to a genetic disease) (table 1). The most common immune-mediated inflammatory demyelinating disease of the central nervous system is multiple sclerosis (MS).

The pathogenesis, pathology, and epidemiology of MS will be reviewed here. Other aspects of MS are discussed separately:

(See "Clinical course and classification of multiple sclerosis".)

(See "Clinical features of multiple sclerosis in adults".)

(See "Diagnosis of multiple sclerosis in adults".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Sep 05, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Weiner HL. Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol 2004; 61:1613.
  2. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372:1502.
  3. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15:545.
  4. Goodin DS. The epidemiology of multiple sclerosis: insights to disease pathogenesis. Handb Clin Neurol 2014; 122:231.
  5. Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest 2012; 122:1180.
  6. Roach ES. Is multiple sclerosis an autoimmune disorder? Arch Neurol 2004; 61:1615.
  7. Lucchinetti C, Brück W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47:707.
  8. Oksenberg JR, Panzara MA, Begovich AB, et al. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 1993; 362:68.
  9. Zhang J, Markovic-Plese S, Lacet B, et al. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 1994; 179:973.
  10. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201:233.
  11. Kebir H, Kreymborg K, Ifergan I, et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 2007; 13:1173.
  12. Tzartos JS, Friese MA, Craner MJ, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008; 172:146.
  13. Petry KG, Boullerne AI, Pousset F, et al. Experimental allergic encephalomyelitis animal models for analyzing features of multiple sclerosis. Pathol Biol (Paris) 2000; 48:47.
  14. Steinman L. Multiple sclerosis. Presenting an odd autoantigen. Nature 1995; 375:739.
  15. Chaudhuri A, Behan PO. Multiple sclerosis is not an autoimmune disease. Arch Neurol 2004; 61:1610.
  16. Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 2004; 55:458.
  17. Matute C, Pérez-Cerdá F. Multiple sclerosis: novel perspectives on newly forming lesions. Trends Neurosci 2005; 28:173.
  18. Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med 2006; 354:942.
  19. Paul F, Wattjes MP. Chronic cerebrospinal venous insufficiency in multiple sclerosis: the final curtain. Lancet 2014; 383:106.
  20. Tsivgoulis G, Faissner S, Voumvourakis K, et al. "Liberation treatment" for chronic cerebrospinal venous insufficiency in multiple sclerosis: the truth will set you free. Brain Behav 2015; 5:3.
  21. Popescu BF, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: where do we stand? Continuum (Minneap Minn) 2013; 19:901.
  22. Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol 2015; 78:710.
  23. Popescu BF, Lucchinetti CF. Pathology of demyelinating diseases. Annu Rev Pathol 2012; 7:185.
  24. Barnard RO, Triggs M. Corpus callosum in multiple sclerosis. J Neurol Neurosurg Psychiatry 1974; 37:1259.
  25. Calabrese M, Filippi M, Gallo P. Cortical lesions in multiple sclerosis. Nat Rev Neurol 2010; 6:438.
  26. Lucchinetti CF, Popescu BF, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 2011; 365:2188.
  27. Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998; 338:278.
  28. Bitsch A, Schuchardt J, Bunkowski S, et al. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 2000; 123 ( Pt 6):1174.
  29. Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 2000; 157:267.
  30. Kutzelnigg A, Lassmann H. Pathology of multiple sclerosis and related inflammatory demyelinating diseases. Handb Clin Neurol 2014; 122:15.
  31. Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 2012; 8:647.
  32. Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005; 128:2705.
  33. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83:278.
  34. Antel J, Antel S, Caramanos Z, et al. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol 2012; 123:627.
  35. Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin 2011; 29:207.
  36. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000; 343:938.
  37. Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008; 71:129.
  38. Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006; 5:932.
  39. Koch-Henriksen N, Sørensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010; 9:520.
  40. Dunn SE, Steinman L. The gender gap in multiple sclerosis: intersection of science and society. JAMA Neurol 2013; 70:634.
  41. Kotzamani D, Panou T, Mastorodemos V, et al. Rising incidence of multiple sclerosis in females associated with urbanization. Neurology 2012; 78:1728.
  42. Karni A, Abramsky O. Association of MS with thyroid disorders. Neurology 1999; 53:883.
  43. Heinzlef O, Alamowitch S, Sazdovitch V, et al. Autoimmune diseases in families of French patients with multiple sclerosis. Acta Neurol Scand 2000; 101:36.
  44. Ramagopalan SV, Dyment DA, Valdar W, et al. Autoimmune disease in families with multiple sclerosis: a population-based study. Lancet Neurol 2007; 6:604.
  45. Marrie RA, Reider N, Cohen J, et al. A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis. Mult Scler 2015; 21:282.
  46. Nielsen NM, Westergaard T, Frisch M, et al. Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study. Arch Neurol 2006; 63:1001.
  47. Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129:819.
  48. Lincoln MR, Montpetit A, Cader MZ, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005; 37:1108.
  49. International Multiple Sclerosis Genetics Consortium, Hafler DA, Compston A, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357:851.
  50. Friese MA, Jakobsen KB, Friis L, et al. Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med 2008; 14:1227.
  51. De Jager PL, Jia X, Wang J, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 2009; 41:776.
  52. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet 2009; 41:824.
  53. International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476:214.
  54. Rubio JP, Stankovich J, Field J, et al. Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun 2008; 9:624.
  55. International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, Patsopoulos NA, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013; 45:1353.
  56. van Luijn MM, Kreft KL, Jongsma ML, et al. Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis. Brain 2015; 138:1531.
  57. Gregory SG, Schmidt S, Seth P, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 2007; 39:1083.
  58. Lundmark F, Duvefelt K, Iacobaeus E, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet 2007; 39:1108.
  59. Ramagopalan SV, Maugeri NJ, 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:e1000369.
  60. Nolan D, Castley A, Tschochner M, et al. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk. Neurology 2012; 79:538.
  61. Cocco E, Meloni A, Murru MR, et al. Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles. PLoS One 2012; 7:e41678.
  62. Sadovnick AD, Armstrong H, Rice GP, et al. A population-based study of multiple sclerosis in twins: update. Ann Neurol 1993; 33:281.
  63. Nielsen NM, Westergaard T, Rostgaard K, et al. Familial risk of multiple sclerosis: a nationwide cohort study. Am J Epidemiol 2005; 162:774.
  64. Ebers GC, Sadovnick AD, Dyment DA, et al. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. Lancet 2004; 363:1773.
  65. Hupperts R, Broadley S, Mander A, et al. Patterns of disease in concordant parent-child pairs with multiple sclerosis. Neurology 2001; 57:290.
  66. Kantarci OH, Barcellos LF, Atkinson EJ, et al. Men transmit MS more often to their children vs women: the Carter effect. Neurology 2006; 67:305.
  67. Herrera BM, Ramagopalan SV, Orton S, et al. Parental transmission of MS in a population-based Canadian cohort. Neurology 2007; 69:1208.
  68. Hoppenbrouwers IA, Liu F, Aulchenko YS, et al. Maternal transmission of multiple sclerosis in a dutch population. Arch Neurol 2008; 65:345.
  69. Herrera BM, Ramagopalan SV, Lincoln MR, et al. Parent-of-origin effects in MS: observations from avuncular pairs. Neurology 2008; 71:799.
  70. Kantarci OH, Spurkland A. Parent of origin in multiple sclerosis: understanding inheritance in complex neurologic diseases. Neurology 2008; 71:786.
  71. Sawcer S, Franklin RJ, Ban M. Multiple sclerosis genetics. Lancet Neurol 2014; 13:700.
  72. Steri M, Orrù V, Idda ML, et al. Overexpression of the Cytokine BAFF and Autoimmunity Risk. N Engl J Med 2017; 376:1615.
  73. Brahic M. Multiple sclerosis and viruses. Ann Neurol 2010; 68:6.
  74. Cusick MF, Libbey JE, Fujinami RS. Multiple sclerosis: autoimmunity and viruses. Curr Opin Rheumatol 2013; 25:496.
  75. Hernán MA, Zhang SM, Lipworth L, et al. Multiple sclerosis and age at infection with common viruses. Epidemiology 2001; 12:301.
  76. Pakpoor J, Giovannoni G, Ramagopalan SV. Epstein-Barr virus and multiple sclerosis: association or causation? Expert Rev Neurother 2013; 13:287.
  77. Thacker EL, Mirzaei F, Ascherio A. Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis. Ann Neurol 2006; 59:499.
  78. Ascherio A, Munger KL, Lennette ET, et al. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. JAMA 2001; 286:3083.
  79. Levin LI, Munger KL, Rubertone MV, et al. Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 2005; 293:2496.
  80. Serafini B, Rosicarelli B, Franciotta D, et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 2007; 204:2899.
  81. Willis SN, Stadelmann C, Rodig SJ, et al. Epstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 2009; 132:3318.
  82. Sargsyan SA, Shearer AJ, Ritchie AM, et al. Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis. Neurology 2010; 74:1127.
  83. Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology 2012; 78:15.
  84. Wandinger K, Jabs W, Siekhaus A, et al. Association between clinical disease activity and Epstein-Barr virus reactivation in MS. Neurology 2000; 55:178.
  85. Larsen PD, Bloomer LC, Bray PF. Epstein-Barr nuclear antigen and viral capsid antigen antibody titers in multiple sclerosis. Neurology 1985; 35:435.
  86. Bray PF, Bloomer LC, Salmon VC, et al. Epstein-Barr virus infection and antibody synthesis in patients with multiple sclerosis. Arch Neurol 1983; 40:406.
  87. Ascherio A, Munch M. Epstein-Barr virus and multiple sclerosis. Epidemiology 2000; 11:220.
  88. Sundström P, Juto P, Wadell G, et al. An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study. Neurology 2004; 62:2277.
  89. Levin LI, Munger KL, O'Reilly EJ, et al. Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol 2010; 67:824.
  90. Alotaibi S, Kennedy J, Tellier R, et al. Epstein-Barr virus in pediatric multiple sclerosis. JAMA 2004; 291:1875.
  91. Waubant E, Mowry EM, Krupp L, et al. Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis. Mult Scler 2013; 19:891.
  92. Sundqvist E, Bergström T, Daialhosein H, et al. Cytomegalovirus seropositivity is negatively associated with multiple sclerosis. Mult Scler 2014; 20:165.
  93. Gilden DH. Infectious causes of multiple sclerosis. Lancet Neurol 2005; 4:195.
  94. Sotelo J, Martínez-Palomo A, Ordoñez G, Pineda B. Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis. Ann Neurol 2008; 63:303.
  95. Kang JH, Sheu JJ, Kao S, Lin HC. Increased risk of multiple sclerosis following herpes zoster: a nationwide, population-based study. J Infect Dis 2011; 204:188.
  96. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347:911.
  97. Ponsonby AL, van der Mei I, Dwyer T, et al. Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA 2005; 293:463.
  98. Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol 2008; 7:268.
  99. Simpson S Jr, Blizzard L, Otahal P, et al. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011; 82:1132.
  100. Dilokthornsakul P, Valuck RJ, Nair KV, et al. Multiple sclerosis prevalence in the United States commercially insured population. Neurology 2016; 86:1014.
  101. Anderson DW, Ellenberg JH, Leventhal CM, et al. Revised estimate of the prevalence of multiple sclerosis in the United States. Ann Neurol 1992; 31:333.
  102. National Multiple Sclerosis Society. MS prevalence. http://www.nationalmssociety.org/About-the-Society/MS-Prevalence (Accessed on December 10, 2016).
  103. Wallin MT, Culpepper WJ, Coffman P, et al. The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service. Brain 2012; 135:1778.
  104. Langer-Gould A, Brara SM, Beaber BE, Zhang JL. Incidence of multiple sclerosis in multiple racial and ethnic groups. Neurology 2013; 80:1734.
  105. Langer-Gould A, Zhang JL, Chung J, et al. Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children. Neurology 2011; 77:1143.
  106. Hernán MA, Olek MJ, Ascherio A. Geographic variation of MS incidence in two prospective studies of US women. Neurology 1999; 53:1711.
  107. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007; 61:504.
  108. van der Mei IA, Ponsonby AL, Dwyer T, et al. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 2003; 327:316.
  109. Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 2007; 69:381.
  110. Orton SM, Wald L, Confavreux C, et al. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Neurology 2011; 76:425.
  111. Ramagopalan SV, Handel AE, Giovannoni G, et al. Relationship of UV exposure to prevalence of multiple sclerosis in England. Neurology 2011; 76:1410.
  112. Salzer J, Hallmans G, Nyström M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012; 79:2140.
  113. Munger KL, Zhang SM, O'Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62:60.
  114. Mokry LE, Ross S, Ahmad OS, et al. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study. PLoS Med 2015; 12:e1001866.
  115. Mowry EM, Waubant E, McCulloch CE, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 2012; 72:234.
  116. Ascherio A, Munger KL, White R, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 2014; 71:306.
  117. Spelman T, Gray O, Trojano M, et al. Seasonal variation of relapse rate in multiple sclerosis is latitude dependent. Ann Neurol 2014; 76:880.
  118. Franklin GM, Nelson L. Environmental risk factors in multiple sclerosis: causes, triggers, and patient autonomy. Neurology 2003; 61:1032.
  119. Riise T, Nortvedt MW, Ascherio A. Smoking is a risk factor for multiple sclerosis. Neurology 2003; 61:1122.
  120. Hernán MA, Jick SS, Logroscino G, et al. Cigarette smoking and the progression of multiple sclerosis. Brain 2005; 128:1461.
  121. Healy BC, Ali EN, Guttmann CR, et al. Smoking and disease progression in multiple sclerosis. Arch Neurol 2009; 66:858.
  122. Zivadinov R, Weinstock-Guttman B, Hashmi K, et al. Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis. Neurology 2009; 73:504.
  123. Manouchehrinia A, Tench CR, Maxted J, et al. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain 2013; 136:2298.
  124. Ramanujam R, Hedström AK, Manouchehrinia A, et al. Effect of Smoking Cessation on Multiple Sclerosis Prognosis. JAMA Neurol 2015; 72:1117.
  125. Hedström AK, Bäärnhielm M, Olsson T, Alfredsson L. Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology 2009; 73:696.
  126. Dobson R, Giovannoni G, Ramagopalan S. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry 2013; 84:427.
  127. Fiddes B, Wason J, Kemppinen A, et al. Confounding underlies the apparent month of birth effect in multiple sclerosis. Ann Neurol 2013; 73:714.
  128. Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology 2013; 80:548.
  129. Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology 2009; 73:1543.
  130. Munger KL, Bentzen J, Laursen B, et al. Childhood body mass index and multiple sclerosis risk: a long-term cohort study. Mult Scler 2013; 19:1323.
  131. Bhargava P, Mowry EM. Gut microbiome and multiple sclerosis. Curr Neurol Neurosci Rep 2014; 14:492.
  132. Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol 2015; 17:344.
  133. Ascherio A, Zhang SM, Hernán MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001; 344:327.
  134. Confavreux C, Suissa S, Saddier P, et al. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med 2001; 344:319.
  135. Hernán MA, Alonso A, Hernández-Díaz S. Tetanus vaccination and risk of multiple sclerosis: a systematic review. Neurology 2006; 67:212.
  136. Rutschmann OT, McCrory DC, Matchar DB, Immunization Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Immunization and MS: a summary of published evidence and recommendations. Neurology 2002; 59:1837.
  137. DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60:504.
  138. Langer-Gould A, Qian L, Tartof SY, et al. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol 2014; 71:1506.
  139. Hernán MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004; 63:838.
  140. Naismith RT, Cross AH. Does the hepatitis B vaccine cause multiple sclerosis? Neurology 2004; 63:772.
  141. Vichnin M, Bonanni P, Klein NP, et al. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015. Pediatr Infect Dis J 2015; 34:983.