Research Article| Volume 311, ISSUE 1-2, P58-63, December 15, 2011

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Why does the north–south gradient of incidence of multiple sclerosis seem to have disappeared on the Northern hemisphere?

  • Nils Koch-Henriksen
    Department of Neurology, Aarhus University Hospital in Aalborg, Denmark

    The Danish Multiple Sclerosis Registry, Neuroscience Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Per Soelberg Sorensen
    Corresponding author at: Danish Multiple Sclerosis Center, Department of Neurology 2082, Rigshospitalet, DK2100 Copenhagen, Denmark.
    Danish Multiple Sclerosis Center, University of Copenhagen and Department of Neurology, Rigshospitalet, Copenhagen, Denmark
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Published:October 10, 2011DOI:


      The traditional view, based on numerous early studies and reviews, is that MS is particularly prevalent in temperate zones both on the northern and southern hemisphere. This uneven distribution of MS can be attributed to differences in genes and environment and their interaction. Diagnostic accuracy and case ascertainment are sources of error and have their shares in the geographical and temporal variations, and improvements in diagnostic accuracy and case ascertainment influence incidence- and prevalence rates. In addition the prevalence also depends on survival. With this meta-analysis we have focused on the trend in the incidence and sex ratio of MS through the last five decades, and we have analyzed the latitudinal distribution of MS incidence, based on a recent literature search. Our findings indicated that the prevalence and incidence rates had increased in almost all areas, but the previously reported latitudinal gradient of incidence of MS in Europe and North America could not be confirmed even when restricting the search to surveys published before 1980 or 1970. Conversely, the latitudinal gradient of prevalence rates seemed to be preserved. This apparent discrepancy can be explained by the circumstance that incidence estimates only depend on complete ascertainment for a relative short recent period of time, whereas reliable prevalence rates presuppose complete ascertainment decades back in time. A contributory explanation for the missing latitudinal gradient for incidence may be changes in environmental factors, levelling out differences in habits of life across Europe and North America, and, not least, that the interpretation of a latitudinal gradient in Europe was based primarily on prevalence studies and reviews.
      In addition, we observed in most regions a profound increase in female incidence of MS. The last observation should prompt epidemiological studies focusing on change in female life style.


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        • Kurtzke J.F.
        Epidemiology of multiple sclerosis. Does this really point toward an etiology? Lectio Doctoralis.
        Neurol Sci. Dec 2000; 21: 383-403
        • Zivadinov R.
        • Iona L.
        • Monti-Bragadin L.
        • Bosco A.
        • Jurjevic A.
        • Taus C.
        • et al.
        The use of standardized incidence and prevalence rates in epidemiological studies on multiple sclerosis. A meta-analysis study.
        Neuroepidemiology. Jan 2003; 22: 65-74
        • Koch-Henriksen N.
        • Sorensen P.S.
        The changing demographic pattern of multiple sclerosis epidemiology.
        Lancet Neurol. May 2010; 9: 520-532
        • Eliasdottir O.J.
        • Olafsson E.
        • Kjartansson O.
        Multiple sclerosis -symptoms, diagnosis and treatment..
        Laeknabladid. Sep 2009; 95: 583-589
        • Vatne A.
        • Mygland Å.
        • Ljøstad U.
        Multiple sclerosis in Vest-Agder county, Norway.
        Acta Neurol Scand. 2011; 123: 396-399
        • Simpson Jr., S.
        • Blizzard L.
        • Otahal P.
        • van dM I.
        • Taylor B.
        Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis.
        J Neurol Neurosurg Psychiatry. Oct 2011; 82: 1132-1141
        • Poskanzer D.C.
        • Prenney L.B.
        • Sheridan J.L.
        • Kondy J.Y.
        Multiple sclerosis in the Orkney and Shetland Islands. I: Epidemiology, clinical factors, and methodology.
        J Epidemiol Community Health. 1980; 34: 229-239
        • Rothwell P.M.
        • Charlton D.
        High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition.
        J Neurol Neurosurg Psychiatry. 1998; 64: 730-735
        • Forbes R.B.
        • Wilson S.V.
        • Swingler R.J.
        The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist?.
        J Neurol. Nov 1999; 246: 1033-1040
        • Sumelahti M.L.
        • Tienari P.J.
        • Wikstrom J.
        • Palo J.
        • Hakama M.
        Increasing prevalence of multiple sclerosis in Finland.
        Acta Neurol Scand. Mar 2001; 103: 153-158
        • Grønlie S.A.
        • Myrvoll E.
        • Hansen G.
        • Grønning M.
        • Mellgren S.I.
        Multiple sclerosis in North Norway, and first appearance in an indigenous population.
        J Neurol. Feb 2000; 247: 129-133
        • Miller D.H.
        • Hornabrook R.W.
        • Dagger J.
        • Fong R.
        Ethnic and HLA patterns related to multiple sclerosis in Wellington, New Zealand.
        J Neurol Neurosurg Psychiatry. 1986; 49: 43-46
        • Polman C.H.
        • Reingold S.C.
        • Edan G.
        • Filippi M.
        • Hartung H.P.
        • Kappos L.
        • et al.
        Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".
        Ann Neurol. Nov 10 2005; 58: 840-846
        • Brønnum-Hansen H.
        • Koch-Henriksen N.
        • Stenager E.
        Trends in survival and cause of death in Danish patients with multiple sclerosis.
        Brain. Apr 2004; 127: 844-850
        • Fawcett J.
        • Skegg D.C.
        Geographic distribution of MS in New Zealand: evidence from hospital admissions and deaths.
        Neurology. 1988; 38: 416-418
        • Taylor B.V.
        • Lucas R.M.
        • Dear K.
        • Kilpatrick T.J.
        • Pender M.P.
        • van der Mai I.
        • et al.
        Latitudinal variation in incidence and type of first central nervous system demyelinating events.
        Mult Scler. Apr 2010; 16: 398-405
        • Cristiano E.
        • Patrucco L.
        • Giunta D.
        • Videla G.
        • Soriano E.R.
        • Rojas J.I.
        Incidence of multiple sclerosis in Buenos Aires: a 16-year health maintenance organization-based study.
        Eur J Neurol. Mar 2010; 17: 479-482
        • Risco J.
        • Maldonado H.
        • Luna L.
        • Osada J.
        • Ruiz P.
        • Juarez A.
        • et al.
        Latitudinal prevalence gradient of multiple sclerosis in Latin America.
        Mult Scler. Sep 2011; 17: 1055-1059
        • Cook S.D.
        • Cromarty J.I.
        • Tapp W.
        • Poskanzer D.
        • Walker J.D.
        • Dowling P.C.
        Declining incidence of multiple sclerosis in the Orkney Islands.
        Neurology. 1985; 35: 545-551
        • Cook S.D.
        • MacDonald J.
        • Tapp W.
        • Poskanzer D.
        • Dowling P.C.
        Multiple sclerosis in the Shetland Islands: an update.
        Acta Neurol Scand. 1988; 77: 148-151
        • Svenningsson A.
        • Runmarker B.
        • Lycke J.
        • Andersen O.
        Incidence of MS during two fifteen-year periods in the Gothenburg region of Sweden.
        Acta Neurol Scand. 1990; 82: 161-168
        • Vukusic S.
        • Van B V.
        • Gosselin S.
        • Confavreux C.
        Regional variations of multiple sclerosis prevalence in French farmers.
        J Neurol Neurosurg Psychiatry. Jul 2007; 78: 707-709
        • Orton S.M.
        • Wald L.
        • Confavreux C.
        • Vukusic S.
        • Krohn J.P.
        • Ramagopalan S.V.
        • et al.
        Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.
        Neurology. Feb 1 2011; 76: 425-431
        • Ebers G.C.
        Environmental factors and multiple sclerosis.
        Lancet Neurol. Mar 2008; 7: 268-277
        • Kalafatova O.
        Geographic and climatic factors and multiple sclerosis in some districts of Bulgaria.
        Neuroepidemiology. 1987; 6: 116-119
        • Kampman M.T.
        • Wilsgaard T.
        • Mellgren S.I.
        Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle.
        J Neurol. Apr 2007; 254: 471-477
        • Munger K.L.
        • Levin L.I.
        • Hollis B.W.
        • Howard N.S.
        • Ascherio A.
        Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.
        JAMA. Dec 20 2006; 296: 2832-2838
        • Kampman M.T.
        • Brustad M.
        Vitamin D: A Candidate for the Environmental Effect in Multiple Sclerosis - Observations from Norway.
        Neuroepidemiology. Apr 2 2008; 30: 140-146
        • Dumas M.
        • Jauberteau-Marchan M.O.
        The protective role of Langerhans' cells and sunlight in multiple sclerosis.
        Med Hypotheses. Dec 2000; 55: 517-520
        • Lucas R.M.
        • Ponsonby A.-L.
        • Dear K.
        • Valery P.C.
        • Pender M.P.
        • Taylor B.V.
        • et al.
        Sun exposure and vitamin D are independent risk factors for CNS demyelination.
        Neurology. Feb 8 2011; 76: 540-548
        • Orton S.M.
        • Herrera B.M.
        • Yee I.M.
        • Valdar W.
        • Ramagopalan S.V.
        • Sadovnick A.D.
        • et al.
        Sex ratio of multiple sclerosis in Canada: a longitudinal study.
        Lancet Neurol. Nov 2006; 5: 932-936
        • Koch-Henriksen N.
        • Stenager E.
        • Brønnum-Hansen H.
        • Flachs E.M.
        Increasing incidence of multiple sclerosis in Danish women.
        Mult Scler. 2006; 12: S228
        • Fasbender P.
        • Kolmel H.W.
        Incidence of Multiple Sclerosis in the Urban Area of Erfurt, Thuringia, Germany.
        Neuroepidemiology. Apr 2 2008; 30: 147-151
        • Debouverie M.
        • Pittion-Vouyovitch S.
        • Louis S.
        • Roederer T.
        • Guillemin F.
        Increasing incidence of multiple sclerosis among women in Lorraine, Eastern France.
        Mult Scler. Jul 10 2007; 254: 1370-1375
        • Midgard R.
        • Riise T.
        • Svanes C.
        • Kvale G.
        • Nyland H.
        Incidence of multiple sclerosis in More and Romsdal, Norway from 1950 to 1991. An age-period-cohort analysis.
        Brain. 1996; 119: 203-211
        • Barnett M.H.
        • Williams D.B.
        • Day S.
        • Macaskill P.
        • McLeod J.G.
        Progressive increase in incidence and prevalence of multiple sclerosis in Newcastle, Australia: a 35-year study.
        J Neurol Sci. Sep 15 2003; 213: 1-6