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Article
May 2, 2018
Letter to the Editor

Incidence of MS has increased markedly over six decades in Denmark particularly with late onset and in women

May 29, 2018 issue
90 (22) e1954-e1963

Abstract

Objective

To describe the pattern of development of incidence of multiple sclerosis (MS) over 60 years in Denmark with age-period-cohort analyses and seasonality of birth.

Methods

Data on virtually all patients with onset of MS have since 1950 been prospectively recorded and kept in the Danish Multiple Sclerosis Registry with multiple sources of notification. Annualized incidence rates per 100,000 were directly standardized to the European Standard Population.

Results

We have registered 19,536 cases with clinical onset of confirmed MS in Denmark from 1950 to 2009. From the 1950–1959 to the 2000–2009 onset period, incidence more than doubled in women, with an increase from 5.91 (95% confidence interval [CI]: 5.60–6.24) to 12.33 (95% CI: 11.91–12.75) per 100,000 per year compared with a modest 24% increase in men from 4.52 (95% CI: 4.24–4.81) to 6.08 (95% CI: 5.79–6.38). With age at onset of 50 years and older, incidence increased with a factor 4.30 in women and 2.72 in men. The female/male sex ratio increased over time and with year of birth. Age-period-cohort analysis revealed a significant birth cohort effect in addition to the age and period effect. We found no statistically significant seasonality of births.

Conclusion

The incidence of MS has doubled in women, most pronounced with late onset, and has only modestly increased in men. Lifestyle changes in the female population that could include fewer childbirths, increased occurrence of obesity, and increased cigarette consumption may have a role.

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Letters to the Editor
24 July 2018
Author response to Dr. Sajedi
Nils Koch-Henriksen, Neurologist| Clinical Institute, Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry

I thank Dr. Sajedi for the comment on our article, [1] and for noting the interesting articles by Sajedi et al. [2-5] My colleagues and I have no explanation for the apparent drop in incidence of MS in Denmark in the 1960-1969 period, but we decided not to discuss any hypotheses which could not be tested by our data (or elsewhere). Countless factors confound the association between time or geography and MS. The way from covariation to causality is long, and a possible biological link between geomagnetic factors and MS remains inexplicable.

  1. Koch-Henriksen N, Thygesen LC, Stenager E, Laursen B, Magyari M. Incidence of MS has increased markedly over six decades in Denmark particularly with late onset and in women. Neurology 2018;90:e1954-e1963.
  2. Sajedi SA, Abdollahi F. Which Environmental Factor Is Correlated with Long-Term Multiple Sclerosis Incidence Trends: Ultraviolet B Radiation or Geomagnetic Disturbances? Mult Scler Int 2017;2017:4960386.
  3. Sajedi SA, Abdollahi F. Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries. BMC Neurol 2012;12:100.
  4. Sajedi SA, Abdollahi F. Multiple Sclerosis and Geomagnetic Disturbances: Investigating a Potentially Important Environmental Risk Factor. In: Ibaraki M, Mori H, eds. Progress in Medical Geology. Newcastle: Cambridge Scholars Publishing, 2016.
  5. Sajedi SA. Time to consider alternative environmental risk factor rather than ultra violet-B for multiple sclerosis. Mult Scler Relat Disord 2018;24:47.

For disclosures, please contact the editorial office at [email protected].

10 July 2018
Important, but neglected, period in the Danish multiple sclerosis registry
Seyed Aidin Sajedi, Head of the Neurology Department| Golestan University of Medical Sciences

The valuable article by Koch-Henriksen et al. depicted the alteration of multiple sclerosis (MS) incidence in the past six decades in Denmark. [1] As the authors stated, their nationwide MS registry showed a notable increase in MS incidence, but they neither discussed nor indicated to the importance of the decreasing trend of MS incidence in Denmark from 1950 to 1964, a fact that is obvious in figure 6. [1] Considering that period, the whole picture of MS incidence seems to be parabolic. Such a wax-and-wane pattern and its turning point are highly valuable for differentiating the potential environmental risk factors, based on their capability to explain it. There is not any evidence that the Danish diet or their food vitamin-D content changed dramatically during that period. Moreover, based on our recent study, the received solar ultra-violet B in Denmark cannot explain this incidence pattern. [2]

Valuable data should not be neglected in favor of current hypotheses. There are other potential environmental risk factors, like geomagnetic disturbances, that may show their capabilities to explain such incidence patterns when researchers consider the data as a whole. [3-5]

  1. Koch-Henriksen N, Thygesen LC, Stenager E, Laursen B, Magyari M. Incidence of MS has increased markedly over six decades in Denmark particularly with late onset and in women. Neurology 2018;90:e1954-e1963.
  2. Sajedi SA, Abdollahi F. Which Environmental Factor Is Correlated with Long-Term Multiple Sclerosis Incidence Trends: Ultraviolet B Radiation or Geomagnetic Disturbances? Mult Scler Int 2017;2017:4960386.
  3. Sajedi SA, Abdollahi F. Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries. BMC Neurol 2012;12:100.
  4. Sajedi SA, Abdollahi F. Multiple Sclerosis and Geomagnetic Disturbances: Investigating a Potentially Important Environmental Risk Factor. In: Ibaraki M, Mori H, eds. Progress in Medical Geology. Newcastle: Cambridge Scholars Publishing, 2016.
  5. Sajedi SA. Time to consider alternative environmental risk factor rather than ultra violet-B for multiple sclerosis. Mult Scler Relat Disord 2018;24:47.

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 90Number 22May 29, 2018
Pages: e1954-e1963
PubMed: 29720546

Publication History

Received: November 15, 2017
Accepted: February 28, 2018
Published online: May 2, 2018
Published in print: May 29, 2018

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Disclosure

N. Koch-Henriksen has received travel expenses and registration fees for attending congresses and meetings from TEVA and Merck, outside the submitted work. L. Caspar Thygesen, E. Stenager, and B. Laursen report no disclosures relevant to the manuscript. M. Magyari reports personal fees from Biogen, grants and personal fees from Teva, personal fees from Merck, grants and personal fees from Novartis, grants and personal fees from Genzyme, and grants from Roche, outside the submitted work. Go to Neurology.org/N for full disclosures.

Study Funding

Study funded by the Danish MS Society.

Authors

Affiliations & Disclosures

Nils Koch-Henriksen, DMSc
From the Clinical Institute (N.K.-H.), Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry (N.K.-H., E.S., M.M.) and Department of Neurology (M.M.), Rigshospitalet, University of Copenhagen; National Institute of Public Health (L.C.T., B.L.), University of Southern Denmark in Copenhagen; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Nils Koch-Henriksen has received travel expenses and registration fees for attending congresses and meetings from TEVA, and Merck, outside the submitted work.
Editorial Boards:
1.
Multiple Sclerosis and Related Disorders (since establishment)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Lau Caspar Thygesen, PhD
From the Clinical Institute (N.K.-H.), Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry (N.K.-H., E.S., M.M.) and Department of Neurology (M.M.), Rigshospitalet, University of Copenhagen; National Institute of Public Health (L.C.T., B.L.), University of Southern Denmark in Copenhagen; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Egon Stenager, MD
From the Clinical Institute (N.K.-H.), Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry (N.K.-H., E.S., M.M.) and Department of Neurology (M.M.), Rigshospitalet, University of Copenhagen; National Institute of Public Health (L.C.T., B.L.), University of Southern Denmark in Copenhagen; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Bjarne Laursen, PhD
From the Clinical Institute (N.K.-H.), Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry (N.K.-H., E.S., M.M.) and Department of Neurology (M.M.), Rigshospitalet, University of Copenhagen; National Institute of Public Health (L.C.T., B.L.), University of Southern Denmark in Copenhagen; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Melinda Magyari, PhD
From the Clinical Institute (N.K.-H.), Department of Clinical Epidemiology, University of Aarhus; Danish Multiple Sclerosis Registry (N.K.-H., E.S., M.M.) and Department of Neurology (M.M.), Rigshospitalet, University of Copenhagen; National Institute of Public Health (L.C.T., B.L.), University of Southern Denmark in Copenhagen; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense.
Disclosure
Scientific Advisory Boards:
1.
(1)Biogen (2)Teva (3) Sanofi (3)Roche (4) Merck (5) Novartis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1)Biogen (2)Teva (3) Sanofi (4)Novartis
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Roche (2) KORA: Det Nationale Institut for Kommuners og Regioners Analyse og Forskning
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1)Biogen (2)Teva (3) Sanofi (3)Roche (4) Merck (5) Novartis
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Koch-Henriksen [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Nils Koch-Henriksen: study concept and design, data acquisition, statistical analyses, interpretation of the results, drafting and revision of the manuscript. Lau Caspar Thygesen: critical review of the age-period-cohort analyses and statistical methods, interpretation of the results, revision of the manuscript. Egon Stenager: study concept, data acquisition, interpretation of the results, revision of the manuscript. Bjarne Laursen: revision of the manuscript and the statistical methods. Melinda Magyari: study concept and design, interpretation of results, revision of the manuscript.

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