Multicenter case-control study of multiple sclerosis and risk factors. Design of study

  • The Coordinating Center
  • the Neurological Centers of the Cooperative Group
Original Articles


We present the design of an Italian multicenter case-control study of multiple sclerosis (MS) promoted by the Neuroepidemiology Section of the Italian Society of Neurology (SIN). The principal objective of the study is to verify the existence of an association between MS and migration from the south to the north of Italy and to assess any such association in causal terms (ethnic origin; environmental factors). A second aim is to explore the association between MS, some viral infections suggested as cause(s) of the disease and other variables reported in the literature. The criteria for case and control definition, for their recruitment and the methods of data collection and analysis are described. To date 1593 subjects, of whom 432 have MS, have been included in the study. The first results will become available early in 1986.


Epidemiology multiple sclerosis migration etiology 


Viene presentato il disegno di uno studio multicentrico italiano di tipo caso-controllo sulla Sclerosi Multipla (S.M.) promosso dalla Sezione di Neuroepidemiologia della Società Italiana di Neurologia (SIN). L'obiettivo principale dello studio è quello di verificare l'esistenza di una associazione tra S.M. e migrazione dal Sud al Nord Italia e valutare questa eventuale associazione in termini causali (origine etnica; fattori ambientali). In secondo luogo si vuole esplorare l'associazione tra S.M., alcune malattie infettive virali ipotizzate come cause/ e della malattia e altre variabili riportate in letteratura.

Vengono descritti i criteri utilizzati per la definizione dei casi, dei controlli e per il loro reclutamento e i metodi di raccolta delle informazioni e di analisi dei dati.

A tutt'oggi sono stati inclusi 1593 soggetti di cui 432 casi di S.M. Entro l'inizio del 1986 saranno disponibili i primi risultati.


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  1. [1]
    Acheson Ed:Epidemiology of multiple sclerosis. Br Med Bull 38, 1: 9–14, 1977Google Scholar
  2. [2]
    Agranoff Bw, Goldberg D.:Diet and the geographical distribution of multiple sclerosis. Lancet 2: 1061–1066, 1974.CrossRefPubMedGoogle Scholar
  3. [3]
    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
  4. [4]
    Alter M, Okihiro M:When is multiple sclerosis acquired? Neurology (Minneap) 21: 1030–1036, 1971.Google Scholar
  5. [5]
    Alter M, Yamoor M, Harshe M:Multiple sclerosis and nutrition. Arch Neurol 31: 267–272, 1974PubMedGoogle Scholar
  6. [6]
    Alter M:Is multiple sclerosis an age dependent host response to measles? Lancet 1: 456–459, 1976CrossRefPubMedGoogle Scholar
  7. [7]
    Alter M:Multiple sclerosis, herpes virus and immunity. Lancet 2: 1224–1225, 1981CrossRefGoogle Scholar
  8. [8]
    Amaducci L, Arfaioli C, Inzitari D et al:Multiple sclerosis among shoe and leather workers: an epidemiological survey in Florence. Acta Neurol Scand 65: 94–103, 1982PubMedGoogle Scholar
  9. [9]
    Andersen E, Isager H, Hyllested K:Risk factors in multiple sclerosis: tuberculin reactivity, age at measles infection, tonsillectomy and appendictomy: Acta Neurol Scand 63: 131–135, 1981PubMedGoogle Scholar
  10. [10]
    Antonovsky A, Leibowitz U, Medalie JM et al:Epidemiological studies on multiple sclerosis in Israel. 3. Multiple sclerosis and socio-economic status. J Neurol Neurosurg Psychiat 30: 1–8, 1967Google Scholar
  11. [11]
    Beebe Gw, Kurtzke Jf, Kurland Lt et al:Studies on the natural history of multiple sclerosis. 3. Epidemiologic analysis of the Army experience in World War II. Neurology (Minneap) 17: 1–17, 1967Google Scholar
  12. [12]
    Borri P, Tavolato Pf, Ballatori E et al.:Epidemiological survey on multiple sclerosis in Italy. Riv Pat Nerv Ment 97: 205–210, 1976.PubMedGoogle Scholar
  13. [13]
    Bramanti P, Messina C, Scuderi D et al:An epidemiological study of multiple sclerosis in the province of Messina, Italy. Acta Neurol (Napoli) 33: 532–539, 1978Google Scholar
  14. [14]
    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
  15. [15]
    Buscaino Ga, Indaco A, Sanna G et al:Indagini epidemiologiche sulla sclerosi a placche in Campania. Acta Neurol (Napoli) 29: 486–502, 1974Google Scholar
  16. [16]
    Cook Sd, Dowling Pc:Distemper and multiple sclerosis in Sitka, Alaska. Ann Neurol 11: 192–194, 1981CrossRefGoogle Scholar
  17. [17]
    Dean G, Kurtzke Jf:On the risk of multiple sclerosis according to the age of immigration to South Africa. Br Med J 3: 725–729, 1971PubMedGoogle Scholar
  18. [18]
    Dean G, McLoughlin H, Brady R et al:Multiple sclerosis among immigrants in Greater London.Br Med J 1: 861–864, 1976PubMedGoogle Scholar
  19. [19]
    Dean G, Grimaldi G, Kelly R et al:Multiple sclerosis in Southern Europe I Prevalence in Sicily in 1975. J Epidemiol Commun Health 33: 107–110, 1979Google Scholar
  20. [20]
    Dean G, Savettieri G, Taibi G et al:The prevalence of multiple sclerosis in Sicily. II; Agrigento city. J Epidemiol Commun Health 35: 118–122, 1981Google Scholar
  21. [21]
    Detels R.:Epidemiology of multiple sclerosis. Adv Neurol 19: 459–473, 1978PubMedGoogle Scholar
  22. [22]
    Fischman Hr:Multiple sclerosis: a two-stage process? Am J Epidemiol 114: 244–252, 1981PubMedGoogle Scholar
  23. [23]
    Fischman Hr:Multiple sclerosis: a new perspective on epidemiologic patterns. Neurology (NY) 32: 864–870, 1982Google Scholar
  24. [24]
    Granieri E, Rosati G:Italy: a medium or high risk area for multiple sclerosis? An epidemiological study in Barbagia, Sardinia, southern Italy. Neurology 32: 466–472, 1982PubMedGoogle Scholar
  25. [25]
    Grufferman S, Delzell E:Epidemiology of Hodgkin's disease. In: Epidemiologic Reviews. Nathanson N, Gordis L, Gregg MB, Szklo M eds Baltimore, USA V6: 76–106, 1984Google Scholar
  26. [26]
    Gruppo di lavoro di neuroepidemiologia:Primi risultati ed indicazioni emergenti dalla indagine nazionale sugli studi neuroepidemiologici, i problemi collegati e le risorse impegnate. In: Atti del III Convegno Nazionale di Neuroepidemiologia. Filippini G, Boeri R ed Milano: XIII–XIX, 1982Google Scholar
  27. [27]
    Gutensohn N, Cole P:Epidemiology of Hodgkin's disease. Semin. Oncol 7: 92–102, 1980PubMedGoogle Scholar
  28. [28]
    Haile Rw, Hodge Se, Iselius L:Genetic susceptibility to multiple sclerosis: a review. Int J Epidemiol 12: 8–16, 1983PubMedGoogle Scholar
  29. [29]
    Haire M, Frazer Kb, Millar Jh:Measles and other virus-specific immunoglobulins in multiple sclerosis. Br Med J 3: 612–615, 1973PubMedGoogle Scholar
  30. [30]
    Kirk J:Pseudoviral hollow-cored vesicles in multiple sclerosis brain. Acta Neuropathol (Berl) 48: 63–66, 1979CrossRefGoogle Scholar
  31. [31]
    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, 1952PubMedGoogle Scholar
  32. [32]
    Kurtzke Jf, Hyllested K:Multiple sclerosis in the Faroe Islands. I Clinical and epidemiological features. Ann Neurol 5: 6–21, 1979CrossRefPubMedGoogle Scholar
  33. [33]
    Kurtzke Jf:Epidemiological contribution to multiple sclerosis, an overview. Neurology (NY) 30 (Suppl 2): 61–79, 1980.Google Scholar
  34. [34]
    Kurtzke Jf, Gudmundsson Kr, Bergmann S:Multiple sclerosis in Iceland. I Evidence of a postwar epidemic. Neurology (NY) 32: 143–150, 1981Google Scholar
  35. [35]
    Kurtzke Jf:Some epidemiological trends in multiple sclerosis. Trends Neurosci 6: 75–80, 1983CrossRefGoogle Scholar
  36. [36]
    Kurtzke Jf:III Migration and the risk of MS. Neurology (NY) 35: 672–678, 1985Google Scholar
  37. [37]
    La Mantia L, Musicco M, Milanese C et al:Multiple sclerosis and immigration A case-control study preliminary report. Acta Neurol Scand 64: 361–369, 1981PubMedGoogle Scholar
  38. [38]
    Larsen Pd, Bloomer Lc, Bray Pf:Epstein-barr nuclear antigen and viral capsid antigen antibody titers in multiple sclerosis. Neurology (NY) 35: 435–438, 1985Google Scholar
  39. [39]
    Leibowitz U, Antonovsky A, Medalie Jm et al:Epidemiological study on multiple sclerosis in Israel. 2 Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiat 29: 60–68, 1966PubMedGoogle Scholar
  40. [40]
    Leibowitz U, Sharon D, Alter M:Geographical considerations in multiple sclerosis. Brain 90: 871–877, 1967.PubMedGoogle Scholar
  41. [41]
    Macchi G, Saginario M, Valla S:La sclérose en plaques dans la province de Parma (Italie). World Neurol 3: 731–739, 1962Google Scholar
  42. [42]
    Marforio S, Rosati G, Granieri E et al:Tavola rotonda su “Ruolo degli studi epidemiologici nella comprensione della eziologia della sclerosis multipla. Problemi metodologici e proposte”. In: Atti del III Convegno Nazionale di Neuroepidemiologia. Filippini G, Boeri R ed Milano: 3–66, 1982.Google Scholar
  43. [43]
    Marforio S.:Criteri di diagnosi e proposta per una classificazione unica. In: Atti del III Convegno Nazionale di Neuroepidemiologia: Milano: 3–6, 1982Google Scholar
  44. [44]
    Martin Jr:Herpes simplex virus types 1 and 2 and multiple sclerosis. Lancet 2: 777–781, 1981CrossRefPubMedGoogle Scholar
  45. [45]
    McCollum Rw:Viral hepatitis. InEvans AS ed.Viral infections of humans: epidemiology and control. Plenum, New York, p 303, 1978Google Scholar
  46. [46]
    McDonald Wl, Halliday Am:Diagnosis and classification of multiple sclerosis. Br Med Bull 33: 4–9, 1977PubMedGoogle Scholar
  47. [47]
    Miller H, Ridley A, Schapira K:Multiple sclerosis: a note on social incidence. Br Med J 2: 343–345, 1960Google Scholar
  48. [48]
    Newell Gr:Etiology of multiple sclerosis and Hodgkin's disease. Am J Epidemiol 91: 119–122, 1970PubMedGoogle Scholar
  49. [49]
    Norrby E.:Viral antibodies in multiple sclerosis. Prog Med Virol 24: 1–39, 1978PubMedGoogle Scholar
  50. [50]
    Okinaka S et al:Multiple sclerosis in Northern and Southern Japan. World Neurol 1: 22–42, 1960Google Scholar
  51. [51]
    Paci A, Borri P:La sclerosi a placche nella regione umbra.Ann Neurol Psichiat 61: 507–520, 1967Google Scholar
  52. [52]
    Rosati G, Granieri E, Carreras M et al:Epidemiologia della sclerosi multipla in piccole comunità dell'Italia Settentrionale ed Insulare. In: Atti del II Convegno Nazionale di Neuroepidemiologia. Filippini G. Boeri R ed Milano: 157–161, 1980Google Scholar
  53. [53]
    Rossi G, Ferrari G, Dalri E:Sclerosi multipla nella provincia di Trento: ricerca epidemiologica. In: Attidel II Convegno Nazionale di Neuroepidemiologia. Milano: 149–152, 1980Google Scholar
  54. [54]
    Savettieri G, Daricello B, Giordano D et al:The prevalence of multiple sclerosis in Sicily, Monreale city. J Epidemiol Commun Health 35: 114–117, 1981Google Scholar
  55. [55]
    Sullivan C, Vischer B, Detels R et al:Multiple sclerosis and later age and childhood diseases: a comparison of cases and friends. Proceedings of the Society for Epidemiologic Research. Abstract of papers presented at the 15th annual meeting. Am J Epidemiol 116: 578, 1982Google Scholar
  56. [56]
    Vassallo L, Elian M, Dean G:Multiple sclerosis in Southern Europe 2: prevalence in Malta in 1978, J Epidemiol Commun Health 33: 111–113, 1979Google Scholar
  57. [57]
    Visscher Br, Bunnel Dh, Detels R:Multiple sclerosis and multiple moves: an etiological hypothesis. Am J Epidemiol 113: 140–143, 1981PubMedGoogle Scholar
  58. [58]
    Wainerdi Hr:Does the multiple sclerosis syndrome begin at puberty? Boston Med Quart 12: 44–47, 1961Google Scholar
  59. [59]
    Warner Hb, Carp Rl:Multiple sclerosis and Epstein-Barr virus. Lancet 2: 1290–1293, 1981.CrossRefGoogle Scholar

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© Masson Italia Periodici S.r.l. 1986

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  • The Coordinating Center
  • the Neurological Centers of the Cooperative Group

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