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Prior medical conditions and the risk of amyotrophic lateral sclerosis

Journal of Neurology volume 261, pages 1949–1956 (2014)Cite this article

Abstract

Sporadic amyotrophic lateral sclerosis (ALS) is believed to be a complex disease in which multiple exogenous and genetic factors interact to cause motor neuron degeneration. Elucidating the association between medical conditions prior to the first symptoms of ALS could lend support to the theory that specific subpopulations are at risk of developing ALS and provide new insight into shared pathogenic mechanisms. We performed a population-based case–control study in the Netherlands, including 722 sporadic ALS patients and 2,268 age and gender matched controls. Data on medical conditions and use of medication were obtained through a structured questionnaire. Multivariate analyses showed that hypercholesterolemia (OR 0.76, 95 % CI 0.63–0.92, P = 0.006), the use of statins (OR 0.45, 95 % CI 0.35–0.59, P = 1.86 × 10−9) or immunosuppressive drugs (OR 0.26, 95 % CI 0.08–0.86, P = 0.03) were associated with a decreased risk of ALS. Head trauma was associated with an increased ALS susceptibility (OR 1.95, 95 % CI 1.11–3.43, P = 0.02). No association was found with autoimmune diseases, cancer, psychiatric disorders or cardiovascular diseases, or survival. The lower frequency of hypercholesterolemia and less use of statins in ALS patients indicate a favorable lipid profile prior to symptom onset in at least a subpopulation of ALS. Prior head trauma is a risk factor for ALS and the significantly lower use of immunosuppressive drugs in ALS patients could suggest a protective effect. The identification of specific subpopulations at risk for ALS may provide clues towards possible pathogenic mechanisms.

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Acknowledgments

The authors thank Hermieneke Vergunst (University Medical Center Utrecht) for technical assistance. This work was supported by the Prinses Beatrix Spierfonds (PB 0703); VSB fonds; H. Kersten and M. Kersten (Kersten Foundation); The Netherlands ALS Foundation; J.R. van Dijk and the Adessium Foundation; Netherlands Organisation for Health Research and Development (Vici scheme to LHvdB); and the European Community’s Health Seventh Framework Programme (FP7/2007–2013) (Grant Agreement No 259867). Sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Conflicts of interest

Dr. Veldink received travel grants from Baxter. Dr. van den Berg received travel grants and consultancy fees from Baxter and served on the advisory board of Biogen. All other authors declare that they have no conflict of interest.

Ethical standard

Ethical approval was obtained from the institutional review board of the University Medical Center Utrecht. All participants gave written informed consent for inclusion in the study.

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Authors and Affiliations

  1. Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Meinie Seelen, Perry T. C. van Doormaal, Anne E. Visser, Mark H. B. Huisman, Margot H. J. Roozekrans, Sonja W. de Jong, Jan H. Veldink & Leonard H. van den Berg

  2. Department of Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Anneke J. van der Kooi & Marianne de Visser

  3. Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Center for Neuroscience, Radboud University Medical Center, Comeniuslaan 4, 6525 HP, Nijmegen, The Netherlands

    Nicol C. Voermans

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  1. Meinie Seelen
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  10. Jan H. Veldink
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Corresponding author

Correspondence to Leonard H. van den Berg.

Additional information

J. H. Veldink and L. H. van den Berg contributed equally to this work.

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Seelen, M., van Doormaal, P.T.C., Visser, A.E. et al. Prior medical conditions and the risk of amyotrophic lateral sclerosis. J Neurol 261, 1949–1956 (2014). https://doi.org/10.1007/s00415-014-7445-1

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