European Journal of Epidemiology

, Volume 32, Issue 10, pp 867–879 | Cite as

Meta-analytic evaluation of the association between head injury and risk of amyotrophic lateral sclerosis

  • Yukari WatanabeEmail author
  • Takamitsu Watanabe


Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case–control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21–1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01–1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84–1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.


Amyotrophic lateral sclerosis Motor neuron disease Head trauma Reverse causation 



We acknowledge Dr Valentina Gallo for her support. TW acknowledges the support from European Commission.

Author contribution

YW designed the study. YW and TW conducted the analyses and wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10654_2017_327_MOESM1_ESM.docx (248 kb)
Supplementary material 1 (DOCX 248 kb)


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Blizard InstituteQueen Mary University of LondonLondonUK
  2. 2.Department of Orthopaedic Surgery, Graduate School of MedicineThe University of TokyoBunkyo-kuJapan
  3. 3.Institute of Cognitive NeuroscienceUniversity College LondonLondonUK

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