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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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 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.
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