The Italian Journal of Neurological Sciences

, Volume 5, Issue 4, pp 347–356 | Cite as

A review of the etiology of multiple sclerosis

  • Vella V. 
Review

Abstract

The geographic distribution of multiple sclerosis and the influence of migration on the risk of contracting it point to an environmental factor as cause of the disease. This environmental factor might be a virus which might produce the demyelination process through an autoimmune reaction against components of the central nervous system. The other possible cause of multiple sclerosis is a genetic susceptibility, inferred from the higher risk for the disease found among relatives of patients with multiple sclerosis and on the association between the disease and some histocompatibility antigens of the HLA system. Both theories seem to be correct, with the environmental factors (s) causing multiple sclerosis only in the presence of a genetic susceptibility.

Key-words

Prevalence cell-mediated immunity HLA 

Sommario

La distribuzione geografica della sclerosi multipla e l'influenza che l'emigrazione ha sul rischio di contrarre la malattia indicano che essa potrebbe essere causata da un fattore ambientale. Questo fattore ambientale potrebbe essere un virus che produrrebbe il processo di demielinizzazione tramite una reazione autoimmunitaria contro componenti del sistema nervoso centrale. L'altra possibile causa della sclerosi multipla sarebbe lapresenza di una predisposizione genetica, comprovata dall'esistenza di unpiù alto rischio per la malattia tra i parenti di malati affetti da sclerosi multipla e dall'associazione trovata tra la malattia ed alcuni antigeni di istocompatibilità del sistema HLA. Ambedue le teorie sembrano corrette, i fattori ambientali causerebbero la sclerosi multipla solo in presenza di una predisposizione genetica.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Kurtzke JF:Epidemiologic contribution to multiple sclerosis, an overview. Neurology (Ny) 30 (7 Pt 2): 61–79, 1980.Google Scholar
  2. [2]
    îean G, Grimaldi G, Kelly R, Karhausen L:Multiple sclerosis in Southern Europe I: prevalence in Sicily in 1975. J Epidemiol Community Health 33: 107–110, 1979.PubMedGoogle Scholar
  3. [3]
    Vassallo L, Elian M, Dean G:Multiple sclerosis in Southern Europe 2: prevalence in Malta in 1978. J Epidemiol Community Health 33: 111–113, 1979.PubMedGoogle Scholar
  4. [4]
    Kurland LT:The frequency and geographic distribution of multiple sclerosis as indicated by mortality statistics and morbidity surveys in the United States and Canada. Amer J Hyg 55: 457–476, 1952.PubMedGoogle Scholar
  5. [5]
    Okinaka S et al:Multiple sclerosis in Northern and Southern Japan. World Neurol 1: 22–42. 1960.Google Scholar
  6. [6]
    Kurtzke JFAn evaluation of the geographic distribution of multiple sclerosis. Acta Neurol Scand (Suppl 19) 42: 91–107, 1966.PubMedCrossRefGoogle Scholar
  7. [7]
    Kinnunen E., Wikstrom J., Porras J., Palo J.:The epidemiology of multiple sclerosis in Finland: Increase of prevalence and stability of foci in high risk areas. Acta Neurol Scand 67: 255–262, 1983.PubMedGoogle Scholar
  8. [8]
    Kurtzke JF.:Some epidemiological trends in multiple sclerosis. Trends Neurosci 6: 75–80, 1983.Google Scholar
  9. [9]
    Dean G., Kurtzke JF.:On the risk of multiple sclerosis according to the age of immigration to South Africa. Br Med J 3: 725–728, 1971.PubMedGoogle Scholar
  10. [10]
    Alter M., Leibowitz U., Speer J.:Risk of multiple sclerosis related to age at migration to Israel. Arch Neurol 15: 234–237, 1966.PubMedGoogle Scholar
  11. [11]
    Alter M., Okihiro M.:When is multiple sclerosis acquired? Neurology (Minneap) 21: 1030–1036, 1971.Google Scholar
  12. [12]
    Dean G., McLoughlin H., Brady R. et al:Multiple sclerosis among immigrants in Greater London. Br Med J 1: 861–864, 1976.PubMedGoogle Scholar
  13. [13]
    Acheson ED., Bachrach CA, Wright FM.:Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiat Scand (Suppl 147) 35: 132–147, 1960.Google Scholar
  14. [14]
    Miller H., Ridley A., Shapira K.:Multiple sclerosis, a note on social incidence. Br Med J 2: 343–345, 1960.PubMedCrossRefGoogle Scholar
  15. [15]
    Antonovsky A., Leibowitz U., Smith HA et al:Epidemiologic study of multiple sclerosis in Israel. Arch Neurol 13: 183–193, 1965.PubMedGoogle Scholar
  16. [16]
    Beebe WG, Kurtzke JF, Kurland LT, et al.:Studies on the natural history of multiple sclerosis. Epidemiologic analysis of the army experience in World War II. Neurology (Minneap) 17: 1–17, 1967.Google Scholar
  17. [17]
    Alter M., Yamoor M., Harshe M.:Multiple sclerosis and nutrition. Arch. Neurol. 31: 267–272, 1974.PubMedGoogle Scholar
  18. [18]
    Cook SD., Dowling PC.:A possible association between house pets and multiple sclerosis. Lancet 1: 980–982, 1977.PubMedGoogle Scholar
  19. [19]
    Jotkowitz S.:Multiple sclerosis and exposure to house pets. JAMA 238: 854, 1977.PubMedGoogle Scholar
  20. [20]
    Cook SD., Natelson BH, Levin BE, Dowling PC:Further evidence for a possible association between house dogs and multiple sclerosis. Ann Neurol 3: 141–143, 1978.PubMedGoogle Scholar
  21. [21]
    Krakowka S., Koestner A.:Canine distemper virus and multiple sclerosis. Lancet 1: 1127–1128, 1978.PubMedGoogle Scholar
  22. [22]
    Leibowitz U., Antonovsky A., Medalie JM. et al:Epidemiological study of multiple sclerosis in Israel. Part 2, Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiat 29: 60–68, 1966.PubMedGoogle Scholar
  23. [23]
    Alter A.:Multiple sclerosis, herpes virus and immunity. Lancet 2: 1224–1225, 1981.PubMedGoogle Scholar
  24. [24]
    Lewin R.:Promising animal model for multiple sclerosis. Science 221 (4618): 1364, 1983.PubMedGoogle Scholar
  25. [25]
    Thormar H.:Multiple sclerosis and Visna. Science 222 (4627): 966, 1983.PubMedGoogle Scholar
  26. [26]
    Kirk J.:Pseudoviral hollow-cored vescicles in multiple sclerosis brain. Acta Neuropathol (Berl) 48: 63–66, 1979.Google Scholar
  27. [27]
    Haase AT., Pagano J., Waksman B., Nathanson N.:Detection of viral genes and their products in chronic neurological diseases. Ann Neurol 15: 119–121, 1984.PubMedGoogle Scholar
  28. [28]
    Haase AT., Ventura P., Gibbs CJ Jr.,Tourtellotte WW.:Measles virus nucleotide sequences: detection by hybridization in situ. Science 212 (4495): 672–675, 1981.PubMedGoogle Scholar
  29. [29]
    Adels BR., Gajdusek C., Gibbs CJ Jr.,Albrecht P., Rogers NG.:Attempts to transmit subacute sclerosing panencephalitis and isolate a measles related agent with a study of the immune response in patients and experimental animals. Neurology (Minneap) 18 (Pt 2): 30–51, 1968.Google Scholar
  30. [30]
    Carp RI., Licursi PC., Merz PA., et al.:Decreased percentage of polymorphonuclear neutrophils in mouse peripheral blood after inoculation with material from multiple sclerosis patients. J Exp Med 136: 618–629, 1972.PubMedGoogle Scholar
  31. [31]
    Maaden DL., Krezlewicz A., Gravell M. et al:Multiple sclerosis associated agent (MSAA): Failure to confirm an association with multiple sclerosis. Neurology (Minneap) 28: 295–299, 1978.Google Scholar
  32. [32]
    Cobill JM., Hughes D., Keith AB. et al:Multiple sclerosis-associated agent: Failure of multiple sclerosis brain and serum to depress the polymorph count in normal mice and mice inoculated with cells containing C/type particles. J Neurol Sci 41: 11–16, 1979.PubMedGoogle Scholar
  33. [33]
    Cohn H., Oger J., Sabouraud O. et al.:Appraisal of the PAM cell effect as a diagnostic test for multiple sclerosis. Ann Neurol 3: 400–402, 1978.PubMedGoogle Scholar
  34. [34]
    Adams JM., Imagawa DT.Measles antibodies in multiple sclerosis. Proc Soc Exp Biol Med III: 562–566. 1962.Google Scholar
  35. [35]
    Brody JA., Sever JL., Edgar A., McNew J.:Measles antibody titers of multiple sclerosis patients and their siblings. Neurology (Minneap) 22: 492–499, 1972.Google Scholar
  36. [36]
    Salmi AA., Panelius M., Norrby E:Multiple sclerosis and measles virus. Lancet 2: 1088–1089, 1972.PubMedGoogle Scholar
  37. [37]
    Norrby E., Link H., Olsson JE et al:Comparison of antibodies against different viruses in cerebrospinal fluid and serum sample from patients with multiple sclerosis. Infect Immun 10: 688–689, 1974.PubMedGoogle Scholar
  38. [38]
    Ammitzboll T., Clausen J.:Measles antibody in serum of multiple sclerosis patients, their children, siblings and parents. Acta Neurol Scand 48: 47–56, 1972.PubMedGoogle Scholar
  39. [39]
    Verjans IE., Theys P., Delmotte P., Carton H.:Clinical parameters and intrathecal IgG synthesis as prognostic features in multiple sclerosis. J Neurol 229: 115–165, 1983.Google Scholar
  40. [40]
    Philips PE., Christian CL.:Myxovirus antibody increases in human connective tissue disease. Science 168: 982–984, 1970.PubMedGoogle Scholar
  41. [41]
    Triger DR., Kurtz JB., MacCallum FO., Wright R.:Raised antibody titres to measles and rubella viruses in chronic active hepatitis. Lancet 1: 665–667, 1972.PubMedGoogle Scholar
  42. [42]
    Haire M., Frazer KB., Millar JH.:Measles and other virus-specific immunoglobulins in multiple sclerosis. Br Med J 3: 612–615, 1973.PubMedCrossRefGoogle Scholar
  43. [43]
    Norrby E.Viral antibodies in multiple sclerosis. Prog Med Virol 24: 1–39, 1978.PubMedGoogle Scholar
  44. [44]
    Bray PF., Bloomer LC. Salmon VC., et al:Epstein-Barr virus infection and antibody synthesis in patients with multiple sclerosis. Arch Neurol 40: 406–408, 1983.PubMedGoogle Scholar
  45. [45]
    Martin JR.:Herpes simplex virus type I and 2 and multiple sclerosis. Lancet 2: 777–781, 1981.PubMedGoogle Scholar
  46. [46]
    Morley DC.:Measles in the developing world. Proc R Soc Med 67: 1112–1115, 1974.PubMedGoogle Scholar
  47. [47]
    McCollum RW.:Viral hepatitis. In Evans AS ed. Viral infections of humans: epidemiology and control. Plenum. New York, p 303, 1978.Google Scholar
  48. [48]
    In AS Evans Ed.Viral infections of humans: epidemiology and control. Plenum. New York, p 215–216, 1978.Google Scholar
  49. [49]
    Foy HM., Gayston JT.:Adenovirus. In Evans AS ed. Viral infections of humans: epidemiology and control. Plenum. New York, p 57, 1978.Google Scholar
  50. [50]
    Woyciechowska JL., Dambrosia J., Tzan N., Madden DL.,Multiple sclerosis antiviral antibodies. Lancet 2: 1461–1462, 1982.PubMedGoogle Scholar
  51. [51]
    Fischman HR.:Multiple sclerosis: a new perspective on epidemiologic patterns. Neurology (Ny) 32: 864–870, 1982.Google Scholar
  52. [52]
    Mattson DH., Roos RP, Arnason BG.:Isoelectric focusing of IgG eluted from multiple sclerosis and subacute sclerosing panencephalitis brains. Nature 287: 335–337, 1980.PubMedGoogle Scholar
  53. [53]
    Kurtzke JF., Hyllested K.:Multiple sclerosis in the Faroe Islands: I. Clinical and epidemiological features. Ann Neurol 5: 6–21, 1979.PubMedGoogle Scholar
  54. [54]
    Cook SD., Dowling PC., Russel WC.:Multiple sclerosis and canine distemper. Lancet 1: 605–606, 1978.PubMedGoogle Scholar
  55. [55]
    Kurtzke JF., Gudmundsson KR., Bergmann S.:Multiple sclerosis in Iceland: I. Evidence of a postwar epidemic. Neurology (Ny) 32: 143–150. 1982.Google Scholar
  56. [56]
    Paterson PY.:The demyelinating diseases: clinical and experimental studies in animals and man. In: Samter M, Talmadge DW, Rose B, Austen KF, Vaughan JH eds. Immunological diseases 3rd ed. Boston: Little Brown 2: 1400–1435. 1978.Google Scholar
  57. [57]
    Kies MW.:Immunology of myelin basic proteins. In: DB Tower ed. The nervous system. New York: Raven Press 1: 637–646, 1975.Google Scholar
  58. [58]
    Raine CS., Traugott U., Stone SH.:Suppression of chronic allergic encephalomyelitis: relevance to multiple sclerosis. Science 201: 445–448, 1978.PubMedGoogle Scholar
  59. [59]
    Brown A., McFarlin DE., Raine CS.:Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Lab Invest 46: 171–185, 1982.PubMedGoogle Scholar
  60. [60]
    Grundke-Iqbal I., Bornstein MB.:Multiple sclerosis: serum gamma globulin and demyelination in organ culture. Neurology (Ny) 30 (7 Pt I): 749–754, 1980.Google Scholar
  61. [61]
    Abramsky O., Lisak, RP., Silberger DH., Pleasure DE.:Antibodies to oligodendroglia in patients with multiple sclerosis. N Engl J Med 297: 1207–1211, 1977.PubMedCrossRefGoogle Scholar
  62. [62]
    Seil FJ:Tissue culture studies of demyelinating disease: A critical review. Ann Neurol 2: 345–355, 1977.PubMedGoogle Scholar
  63. [63]
    Page N, Perruisseau G, Steck AJ:Binding properties of cerebrospinal fluid IgG in multiple sclerosis and other neurological diseases. J Neurol Sci 60: 23–30, 1983.PubMedGoogle Scholar
  64. [64]
    Traugott U, Snyder S, Raine CS:Oligodendrocyte staining by multiple sclerosis serum is non specific Ann Neurol 6: 13–20, 1979.PubMedGoogle Scholar
  65. [65]
    Kennedy PG, Lisak RP:A search for antibodies against glial cells in the serum and cerebrospinal fluid of patients with multiple sclerosis and Guillain-Barré syndrome. J Neurol Sci 44: 125–133, 1979.PubMedGoogle Scholar
  66. [66]
    Panitch HS, Hooper CJ, Johnson KP:CSF antibody to myelin basic protein. Measurement in patients with multiple sclerosis and subacute sclerosing panencephalitis. Arch Neurol 37: 206–209, 1980.PubMedGoogle Scholar
  67. [67]
    Cook SD, Menonna J, Dowling PC:Serologic abnormalities in multiple sclerosis. Neurology (Minneap) 28 (9 Pt 2): 129–131, 1978.Google Scholar
  68. [68]
    Lund GA, Arnadottir, T, Hukkanen V et al:Characterization of immune complex radioimmunoassay. J Neuroimmunol 4: 253–264, 1983.PubMedGoogle Scholar
  69. [69]
    Noronha ABC, Antel JP, Roos RP, Medof ME:Circulating immune complexes in neurologic disease. Neurology (Ny) 31: 1402–1407 1981.Google Scholar
  70. [70]
    Gorny MK, Wroblewska Z, Pleasure D, et al:CSF antibodies to myelin basic protein and oligodendrocytes in multiple sclerosis and other neurological diseases. Acta Neurol Scand 67: 338–347, 1983.PubMedCrossRefGoogle Scholar
  71. [71]
    Lhermitte F, Lyon CO:La sclérose en plaques. Etat actuel des recherches. 2. Rev Neurol (Paris) 139: 395–406, 1983.Google Scholar
  72. [72]
    Antel JP, Arnason BGW, Medof ME:Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Ann Neurol 5: 338–342, 1979.PubMedGoogle Scholar
  73. [73]
    Reinherz EL, Weiner HL Hauser SL et al:Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies. N Engl J Med 303: 125–129, 1980.PubMedCrossRefGoogle Scholar
  74. [74]
    Sandberg WMLymphocyte populations in the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis and optic neuritis. Scand J Immunol 17: 575–581, 1983.PubMedGoogle Scholar
  75. [75]
    Salonen, R Ilonen J, Reunanen M et al:PPD-PWM-PHA-induced Interferon in stable multiple sclerosis: association with HLA-Dw2 antigen and clinical variables. Ann Neurol 11: 279–284, 1982.PubMedGoogle Scholar
  76. [76]
    Lisak RP,Multiple sclerosis: immunological aspects. Ann Clin Lab Sci 5: 324–329, 1975.PubMedGoogle Scholar
  77. [77]
    Adams CW:Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 33: 15–20, 1977.PubMedGoogle Scholar
  78. [78]
    Lisak RP, Zweiman B:In vitro and in vivo immune responses to homologous myelin basic protein in experimental allergic encephalomyelitis. Cell Immunol II: 212–220, 1974.Google Scholar
  79. [79]
    Falk GA, Kies MW, Alvord EC Jr:Delayed hypersensitivity to myelin basic protein in the passive transfer of experimental allergic encephalomyelitis. J Immun 101: 638–644, 1968.PubMedGoogle Scholar
  80. [80]
    Pettinelli CB McFarlin DE:Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt1+2-T lymphocytes. J Immun 127: 1420–1423, 1981.PubMedGoogle Scholar
  81. [81]
    Lisak RP, Zweiman B:In vitro cell-mediated immunity of cerebrospinal fluid lymphocytes to myelin basic protein in primary demyelinating disease. N Engl J Med 297: 850–853, 1977.PubMedCrossRefGoogle Scholar
  82. [82]
    Lassmann H:Chronic relapsing experimental allergic encephalomyelitis, its value as an experimental model for multiple sclerosis. J Neurol 229: 207–220, 1983.PubMedGoogle Scholar
  83. [83]
    Schapira K, Poskanzer DC, Miller H:Familial and conjugal multiple sclerosis. Brain 86: 315–332, 1963.PubMedGoogle Scholar
  84. [84]
    Mackay RP, Myrianthopoulos NC:Multiple sclerosis in twins and their relatives. Arch Neurol 15: 449–462, 1966.PubMedGoogle Scholar
  85. [85]
    Sadovnick AD:The familial nature of multiple sclerosis. Neurology (Ny) 33: 117, 1983.Google Scholar
  86. [86]
    Cendrowski WS:Multiple sclerosis: discordance in three pairs of dizygotic twins. J Med Genet 5: 266–268, 1968.PubMedGoogle Scholar
  87. [87]
    Williams A, Eldridge R, McFarland H, Houff S, Krebs H, McFarlin D:Multiple sclerosis in twins. Neurology (Ny) 30: 1139–1147, 1980.Google Scholar
  88. [88]
    Sadovnick AD:Concordance in twins and recurrence in sibship in multiple sclerosis. Lancet 1: 1068, 1982Google Scholar
  89. [89]
    Naito S, Namerow N, Mickey MR et al.:Multiple sclerosis: association with HLA-A3. Tissue Antigens 2: 1–4, 1972.PubMedCrossRefGoogle Scholar
  90. [90]
    Jersild C, Svejgaard A, Fog T:HLA antigens and multiple sclerosis. Lancet I: 1240–1241, 1972.Google Scholar
  91. [91]
    Platz P, Ryder LP, Nielsen LS et al.:HLA and idiopathic optic neuritis. Lancet 1: 520–521, 1975.PubMedGoogle Scholar
  92. [92]
    Paty DW, Dossetor JB, Stiller CR et al:HLA in multiple sclerosis. Relationship to measles antibody, mitogen responsiveness and clinical course. J Neurol Sci 32: 371–379, 1977.PubMedGoogle Scholar
  93. [93]
    Jersild C, Fog T, Hansen GS, et al.:Histocompatibility determinants in multiple sclerosis with special reference to clinical course. Lancet 2: 1221–1225, 1973.PubMedGoogle Scholar
  94. [94]
    Opelz G, Terasaki, P, Myers L, et al.:The association of HLA antigens A3, B7 and DW2 with 330 multiple sclerosis patients in the United States. Tissue Antigens 9: 54–58, 1977.PubMedCrossRefGoogle Scholar
  95. [95]
    Compston DAS, Batchelor JR, McDonald WI:B-lymphocyte alloantigens associated with multiple sclerosis. Lancet 2: 1261–1265, 1976.PubMedGoogle Scholar
  96. [96]
    Terasaki PI, Park MS, Opelz G, Ting A:Multiple sclerosis and high incidence of a B lymphocyte antigen. Science 193 (4259): 1245–1247, 1976.PubMedGoogle Scholar
  97. [97]
    Wernet P:Human Ia type alloantigens: methods of detection, aspects of chemistry and biology, markers for disease states. Transplant Rev 30: 294, 1976.Google Scholar
  98. [98]
    McAlpine, Lumsden CE, Archeson, ED:In Multiple Sclerosis: A Reappraisal. Edinburgh & London: Churchill Livingstone. 1972.Google Scholar
  99. [99]
    Brautbar C, Alter M, Kahana E:HLA antigens in multiple sclerosis. Neurology (Minneap) 26 (6 Pt 2): 50–53, 1976.Google Scholar
  100. [100]
    Zibetti A, Cazzullo CL, Smeraldi E, ScorzaSmeraldi R:HLA typing on Italian multiple sclerosis population. Boll Ist Sieroter Milano 56: 539–543, 1978.Google Scholar
  101. [101]
    Ercilla MG et al.:HLA determinants in multiple sclerosis. Tissue Antigens 10: 189, 1977.Google Scholar
  102. [102]
    Kurdi A, Ayesh I, Abdallat A et al.:Different B lymphocyte alloantigens associated with multiple sclerosis in Arabs and North Europeans. Lancet 1: 1123–1125, 1977.PubMedGoogle Scholar
  103. [103]
    Batchelor JR Compston A, McDonald WI:The significance of the association between HLA and multiple sclerosis. Br Med Bull 34: 279–284. 1978.PubMedGoogle Scholar
  104. [104]
    Stewart GJ, Basten A, Kirk, RL:Strong linkage disequilibrium between HLA-DW2 and BfS in multiple sclerosis and in the normal population. Tissue Antigens 14: 86–97, 1979.PubMedCrossRefGoogle Scholar
  105. [105]
    Fielder AHL, Batchelor JR, Vakarelis BN, Compston DAS, McDonald WI:Optic neuritis and multiple sclerosis: do factor B alleles influence progression of disease? Lancet 2: 1246–1248. 1981.PubMedGoogle Scholar
  106. [106]
    Bertrams J:Factor B alleles and multiple sclerosis. Lancet 1: 288, 1982.PubMedGoogle Scholar
  107. [107]
    Roberts DF, Roberts MJ Poskanzer DC:Genetic analysis of multiple sclerosis in Shetland. J Epidemiol Community Health 37: 281–285, 1983.PubMedGoogle Scholar
  108. [108]
    Compston A, Howard S:HLA typing in multiple sclerosis. Lancet 2: 661, 1982.PubMedGoogle Scholar
  109. [109]
    Ebers GC, Paty DW, Stiller CR, Nelson R.F. et al.:HLA-typing in multiple sclerosis sibling pairs. Lancet 2: 88–90. 1982.PubMedGoogle Scholar
  110. [110]
    McDonald WI:Multiple sclerosis: the present position. Acta Neurol Scand 68: 65–76. 1983.PubMedCrossRefGoogle Scholar
  111. [111]
    Poskanzer DC, Prenney LB, Sheridan JL, Kondy JY:Multiple sclerosis in the Orkney and Shetland Islands I: Epidemiology clinical factors and methodology. J Epidemiol Community Health 34: 229–239, 1980.PubMedGoogle Scholar
  112. [112]
    McFarlin DE, McFarland HF:Multiple sclerosis. First of two parts. N Engl J Med 307: 1183–1187, 1982.PubMedCrossRefGoogle Scholar
  113. [113]
    Williams A, Eldridge R, McFarland H, Houff S et al:Multiple sclerosis in twins. Neurology (Ny) 30: 1139–1147, 1980.Google Scholar
  114. [114]
    Poskanzer DC Terasaki PI, Prenney LB et al:Multiple sclerosis in the Orkney and Shetland Islands. 3:Histocompatibility determinants. J Epidemiol Community Health 34: 253–257. 1980.PubMedCrossRefGoogle Scholar
  115. [115]
    Haile RW, Hodge SE, Iselius L:Genetic susceptibility to multiple sclerosis: A review. Int J Epidemiol 12: 8–16, 1983.PubMedGoogle Scholar
  116. [116]
    Detels R, Brody JA, Edgar AH:Multiple sclerosis among American, Japanese and Chinese migrants to California and Washington. J Chronic Dis 25: 3–10, 1972.PubMedGoogle Scholar
  117. [117]
    Traichel JA:Viral switch for autoimmunity. Science News 123: 279, 1983.PubMedGoogle Scholar
  118. [118]
    Webb HE, Fazakerley JK:Can viral envelope glycolipids produce auto-immunity, with reference to the CNS and multiple sclerosis?. Neuropathol Appl Neurobiol 10: 1–10, 1984.PubMedCrossRefGoogle Scholar
  119. [119]
    Kelly WR, Blakemore WF, Jagelman S, Webb HE:Demyelination induced in mice by a virulent Semliki Forest Virus. 2. An ultrastructural study of focal demyelination in the brain. Neuropathol Appl Neurobiol 8: 43–53, 1982.PubMedGoogle Scholar
  120. [120]
    Pathak S Illavia SJ, Webb HE:The identification and role of cells involved in CNS demyelination in mice after Semliki Forest Virus infection: an ultrastructural study. Immunology of nervous system. Prog Brain Res 59: 237–254. 1983.PubMedCrossRefGoogle Scholar
  121. [121]
    Detels R:InAdvances in Neurology vol 19, Neurological Epidemiology” B Schoenberg ed. Raven Press, New York, p 459–473, 1978.Google Scholar
  122. [122]
    Detels R:Case-control studies of multiple sclerosis. Neuroepidemiology 1: 115–123. 1982.Google Scholar

Copyright information

© Masson Italia Periodici S.r.l. 1984

Authors and Affiliations

  • Vella V. 
    • 1
  1. 1.Roma

Personalised recommendations