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Cited by 279Amyotrophic Lateral Sclerosis ResearchTraumatic Brain Injury ResearchSports injuries and prevention

The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index; none of the 10 sources its claims cite is checked for support yet.

Head Injury and Amyotrophic Lateral Sclerosis

Open access
Chen, H., Richard, M., Sandler, D. P., Umbach, D. M., Kamel, F.·2007·American Journal of Epidemiology
DOI 10.1093/aje/kwm153PMC PMC2239342
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Abstract

Recent data showed that soccer players in Italy had an unusually high risk of amyotrophic lateral sclerosis (ALS) and that repeated head trauma might have contributed to this increase. The authors examined whether head injury was related to ALS risk in a case-control study of 109 New England ALS cases diagnosed in 1993-1996 and 255 matched controls. They also conducted a meta-analysis of the published literature. Overall, ever having experienced a head injury was nonsignificantly associated with a higher ALS risk. When compared with persons without a head injury, a statistically significant ALS risk elevation was found for participants with more than one head injury (odds ratio (OR) = 3.1, 95 percent confidence interval (CI): 1.2, 8.1) and patients who had had a head injury during the past 10 years (OR = 3.2, 95 percent CI: 1.0, 10.2). For participants who had had multiple head injuries with the latest occurring in the past 10 years, risk was elevated more than 11-fold. The meta-analysis also indicated a moderately elevated risk of ALS among persons with previous head injuries (OR = 1.7, 95 percent CI: 1.3, 2.2). In this study population, physical injuries to other body parts, including the trunk, arms, or legs, were not related to ALS risk. These data support the notion that head injury may increase the risk of ALS.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a New England case-control study, head injury was not significantly associated with ALS overall, but repeated head injuries and recent head injuries were associated with higher ALS risk. A meta-analysis of published studies plus the current study found a pooled odds ratio of 1.7 for ALS among persons with previous head injury.

Key findings

  • Ever having had a head injury was nonsignificantly associated with ALS (adjusted OR = 1.4, 95% CI: 0.8, 2.6).
  • ALS risk was elevated for more than one head injury (adjusted OR = 3.1, 95% CI: 1.2, 8.1) and for head injury in the past 10 years (adjusted OR = 3.2, 95% CI: 1.0, 10.2); multiple head injuries with the latest in the past 10 years showed more than an 11-fold higher risk (adjusted OR = 11.3, 95% CI: 1.1, 114.3).
  • The meta-analysis found a pooled OR of 1.7 (95% CI: 1.3, 2.2; p < 0.001) for ALS among persons with previous head injuries.
  • Injuries to other body sites, including trunk, arms, or legs, were not related to higher ALS risk.

Methods

  • Case-control study of 109 ALS cases diagnosed in 1993–1996 from two New England referral centers and 255 frequency-matched controls; structured questionnaire assessed injuries severe enough to require medical attention, with unconditional logistic regression adjusted for matching factors, smoking, and education.
  • Meta-analysis of published studies since 1980 identified through MEDLINE and reference lists; one study was excluded because a risk estimate could not be calculated, and a fixed-effects model was used because no statistical heterogeneity was found (p for heterogeneity = 0.1).

Limitations

  • The paper states that cases were interviewed in person and controls by telephone, raising concern about potential bias; analyses were limited by small sample sizes, so chance cannot be excluded; exposure assessment was not independently validated; the meaning of “severe injury” was open to interpretation; and defining head injury as requiring medical attention may limit generalizability.
  • Evident from the text: the 11-fold estimate came from a post-hoc exploratory analysis based on small numbers, and in the meta-analysis, except for the current study, risk estimates were not adjusted for potential confounders and nearly all studies lacked sufficient details for further analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/aje/kwm153

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 10 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the New England case-control study, participants who had had multiple head injuries with the latest occurring in the past 10 years had more than an 11-fold higher ALS risk than those without a head injury.

    “For participants who had had multiple head injuries with the latest occurring in the past 10 years, risk was elevated more than 11-fold.”
    • Also stated in: § Head Injury and ALS 811 · hedged
      “A post-hoc exploratory analysis based on small numbers showed that persons who had experienced repeated head injuries with the latest occurring in the past 10 years had more than an 11-fold higher ALS risk than those without a head injury.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.
  • Findingown data

    In the New England case-control study, patients who had had a head injury during the past 10 years had a statistically significant higher ALS risk (OR 3.2, 95% CI 1.0, 10.2).

    “and patients who had had a head injury during the past 10 years (OR ¼ 3.2, 95 percent CI: 1.0, 10.2).”
    • Also stated in: § Head Injury and ALS 811 · hedged
      “Detailed analyses (table 2) indicated that having experienced repeated head injuries or having been injured within the 10 years before diagnosis was associated with a more than threefold higher risk of ALS (OR ¼ 3.1 (95 percent CI: 1.2, 8.1) and OR ¼ 3.2 (95 percent CI: 1.0, 10.2), respectively).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.
  • Findingown data

    In the New England case-control study, ALS cases with previous head injury were more likely to have a bulbar onset than cases without previous head injury (33.3% vs. 22.4%; p = 0.3).

    “Finally, cases with head injuries were more likely to have a bulbar onset (33.3 percent vs. 22.4 percent; p ¼ 0.3)”
    • Also stated in: § DISCUSSION · plain
      “Consistent with the recent reports on ALS among Italian soccer players (4, 5), ALS cases with a previous head injury were more likely to have an early and bulbar onset.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.
  • Findingown data

    In the New England case-control study, ALS cases with previous head injury had an earlier age of diagnosis than cases without previous head injury (54.0 years vs. 59.5 years; p = 0.05).

    “and an earlier age of diagnosis than cases without previous head injuries (54.0 years vs. 59.5 years; p ¼ 0.05).”
    • Also stated in: § DISCUSSION · hedged
      “Consistent with the recent reports on ALS among Italian soccer players (4, 5), ALS cases with a previous head injury were more likely to have an early and bulbar onset.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.
  • Findingown data

    In the New England case-control study, ever having experienced a head injury was nonsignificantly associated with a higher ALS risk (OR 1.4, 95% CI 0.8, 2.6).

    “Overall, ever having experienced a head injury was nonsignificantly associated with a higher ALS risk.”
    • Also stated in: § Head Injury and ALS 811 · hedged
      “Among individual body sites, only head injury tended to be associated with a higher risk of ALS (odds ratio (OR) ¼ 1.4, 95 percent confidence interval (CI): 0.8, 2.6), but the association was not statistically significant.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.
  • It may state two separate claims as one. 11
  • Probably not a substantial claim. 4

  • It may state two separate claims as one.

    Findingown data

    Among the four cases with repeated head injuries with the latest occurring in the 10 years before diagnosis, three (75%) had a bulbar onset, a proportion significantly greater than among cases without head injuries (Fisher's exact test p < 0.05).

    “Interestingly, three of the four cases (75 percent) with repeated head injuries with the latest occurring in the 10 years before diagnosis had a bulbar onset, and despite the small sample size, the proportion was significantly greater than that among cases without head injuries (Fisher's exact test: p < 0.05).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.

  • Probably not a substantial claim.

    Study design and conductown data

    Controls were frequency-matched to cases by age, gender, and telephone area code.

    “Controls were frequencymatched to cases by age (30-55, 56-65, and 66-80 years), gender, and telephone area code (as a surrogate for region within New England), at a ratio of 3:1 for the Boston area and 2:1 for other areas in New England.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    In this case-control study, head injury was associated with an elevated risk of ALS, particularly for recent repeated head injuries.

    “In this case-control study, head injury was associated with an elevated risk of ALS, particularly for recent repeated head injuries.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Premisecitation

    The only prospective study included 821 patients with documented head injury, but only one ALS patient was identified during follow-up.

    “The only prospective study included 821 patients with documented head injury, but only one ALS patient was identified during follow-up (17).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim.

    Study design and conductown data

    The study conducted multivariate analyses to adjust for several potential confounders.

    “Finally, we conducted multivariate analyses to adjust for several potential confounders.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Premisecitation

    An incidence study among 7,325 Italian professional soccer players who played between 1970 and 2001 found ALS incidence 6.5 times higher than expected, with cases clinically characterized by early onset and bulbar involvement at diagnosis.

    “This finding was subsequently confirmed by an incidence study carried out among 7,325 Italian professional soccer players who had played between 1970 and 2001 (5).The incidence of ALS was 6.5 times higher than expected, and cases were clinically characterized by early onset and bulbar involvement at diagnosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • It may state two separate claims as one.

    Study design and conductown data

    The statistical analyses were limited by small sample sizes, so chance cannot be excluded as a potential explanation for the findings.

    “As with many of the previous studies, the statistical analyses were limited by small sample sizes.Therefore, we cannot exclude chance as a potential explanation for the findings.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Recent findings from clinical observations of asymptomatic SOD1 mutant carriers and experimental studies of SOD1 mutant mice suggest that preclinical motor neuron loss in ALS may be dramatic and aggressive, indicating the importance of recent acute or cumulative exposure as opposed to exposure in the distant past.

    “Recent findings from both clinical observations of asymptomatic SOD1 mutant carriers (18) and experimental studies of SOD1 mutant mice (19) suggest that the preclinical motor neuron loss in ALS, like its postdiagnosis clinical course, may be dramatic and aggressive, indicating the importance of recent acute exposure or cumulative exposure as opposed to exposure in the distant past.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [19]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • It may state two separate claims as one.

    Premisecitation

    Recent data showed that ALS mortality among Italian professional soccer players was approximately 12-fold higher than expected, while mortality from other causes was generally lower than or comparable to that of the general population.

    “Recent data showed that ALS mortality among Italian professional soccer players was approximately 12-fold higher than expected (4), while mortality from other causes was generally lower than or comparable to that of the general population.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • It may state two separate claims as one.

    Interpretationown data

    The detailed analyses from the study support the link between head injury and ALS and further suggest that recent repeated injuries may be more etiologically relevant.

    “Consistently, the detailed analyses from our study support this link and further suggest that recent repeated injuries may be more etiologically relevant.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductnone given

    Exposure assessment in the study was not independently validated, and the meaning of severe injury was open to individual interpretation.

    “Finally, exposure assessment in the current study was not independently validated, and the meaning of severe injury was, to some extent, open to individual interpretation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationnone given

    The definition of head injury as an injury requiring medical attention may limit the generalizability of the findings.

    “Furthermore, the definition of head injury as an injury requiring medical attention may limit the generalizability of our findings somewhat.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationcitation

    Significant recall bias is not a likely explanation for the results, since antecedent reports more frequently implicated injuries involving the shoulders and arms.

    “By the same token, significant recall bias is not a likely explanation for our results, since antecedent reports more frequently implicated injuries involving the shoulders and arms (12, 13)-findings which might have been more publicized among patients.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [13]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    Clinical observations and case-control studies have suggested that physical trauma may be associated with a higher risk of ALS, but the evidence is far from conclusive.

    “Clinical observations and case-control studies have suggested that physical trauma may be associated with a higher risk of ALS, but the evidence is far from conclusive (3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

14 of 14

  • The paper relies on this without support.

    Self-reported severe head injury requiring medical attention accurately reflects true head injury exposure.

    “Finally, exposure assessment in the current study was not independently validated, and the meaning of severe injury was, to some extent, open to individual interpretation.”

  • The paper relies on this without support.

    The unadjusted risk estimates from the published studies included in the meta-analysis are valid enough to combine into a summary estimate.

    “Except in the current study, risk estimates were not adjusted for potential confounders.”

  • The paper relies on this without support.

    The New England case-control study population is representative enough to generalize the observed association to the American population.

    “In summary, in line with the recent observations of higher ALS risk among Italian soccer players, we found that recent repeated head injury was related to a higher risk of ALS in an American population.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Chen et al found individuals were 11 times more likely to develop ALS if they reported multiple head injuries within last 10 years prior to diagnosis.

    “Chen et al found that individuals were 11 times more likely to develop ALS if they reported multiple head injuries within the last 10 years prior to diagnosis (14), although other studies have not found a modifying effect of head injury on ALS (15).”

    From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [14]

    The results (p. 811) report more than an 11-fold higher ALS risk among people with repeated head injuries whose latest injury occurred within 10 years before diagnosis. The claim implies that the multiple injuries all occurred within that period and omits that the estimate came from a post-hoc exploratory analysis based on small numbers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Some studies in a meta-analysis of head injury and ALS may have been influenced by recall bias.

    “Chen et al. (10) reported a significant association for head injury overall in a meta-analysis of eight studies; however, some of the studies in the meta-analysis may have been influenced by recall bias.”

    From Severe head injury and amyotrophic lateral sclerosis (2013) · cites this paper as [10]

    The results section (p. 811) reports a significant association in the meta-analysis, and the discussion (p. 813) says previous studies had a variety of limitations. But the paper does not specifically say that studies in the meta-analysis may have been influenced by recall bias; it says significant recall bias is unlikely to explain its own results. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Some studies have reported that multiple head injuries and age at first head injury were associated with ALS, which is consistent with the findings we observed in our study.

    “Some studies have reported that multiple head injuries and age at first head injury were associated with ALS, which is also consistent with the findings we observed in our study [18,20,61,62].”

    From Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry (2025) · cites this paper as [20]

    The results (p. 811) report that repeated head injuries were associated with higher ALS risk. The Statistical analysis section and Table 2 (p. 813) examine age at the last injury, not age at the first head injury, so this source does not support that part of the claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • TBI may be an environmental risk factor for ALS.

    “One such environmental risk factor may be traumatic brain injury (TBI).Chen et al found that individuals were 11 times more likely to develop ALS if they reported multiple head injuries within the last 10 years prior to diagnosis (14)”

    From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [14]

  • Head injuries have previously been associated with ALS risk.

    “and head injuries (14;20–22).”

    From Association of ALS with head injury, cigarette smoking and APOE genotypes (2010) · cites this paper as [21]

Citations

Cites

Flagged first, then by citations

1 of the 35 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Deapen DM, Henderson BE. A case-control study of amyo- trophic lateral sclerosis. Am J Epidemiol 1986;123:790-9.

Cited by

Sorted by citations

Related

Metadata

Authors
Chen, H., Richard, M., Sandler, D. P., Umbach, D. M., & Kamel, F.
Affiliations
  • National Institutes of Health (US)
  • Westat (United States) (US)
  • National Institute of Environmental Health Sciences (US)
ORCID
Venue
American Journal of Epidemiology
Publisher
Oxford University Press (OUP)
Published
2007-06-27
Volume
166
Issue
7
Pages
810-816
ISSN
  • 0002-9262 (ISSN-L)
  • 1476-6256
DOI
10.1093/aje/kwm153
PMC
PMC2239342
OpenAlex
W2152476219
Cited by
279
References
35
Citations by year
2026: 8 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 19 · 2020: 19 · 2019: 16 · 2018: 19 · 2017: 19 · 2016: 24 · 2015: 25 · 2014: 18 · 2013: 12 · 2012: 13
FWCI
5.76
Type
journal article
Language
en
Open access
Locations
  • American Journal of Epidemiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (Z01-ES049005)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports injuries and prevention
Keywords
amyotrophic lateral sclerosis, traumatic brain injury, repeated head trauma, ALS risk factors, soccer players, sports injuries
MeSH terms
Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Female, Craniocerebral Trauma, Humans, Life Style, Male, Middle Aged, New England, Risk Factors, Soccer, Confidence Intervals, Odds Ratio, Case-Control Studies, Risk Assessment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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