Appendix for: Light chain neurofilament revealing brain tissue damage in physical contact sport athletes, a systematic review

Objective: To evaluate whether participating in physical contact
sports is associated with a release of neurofilaments and whether this
release is related to future clinical neurological and/or psychiatric
impairment. Methods: We have performed a systematic literature
review of the PubMed, MEDLINE and Cochrane Library databases using a
combination of the search terms neurofilament(s)/intermediate filament and
sport(s)/athletes. Only original studies, written in English, that have
reported on neurofilament measurements in CSF and/or serum/plasma of
physical contact sport athletes were retained for data extraction. This
review was conducted following the Preferred Reporting Items for
Systematic Review and Analyses guidelines. Results: Eighteen
studies reporting on light chain neurofilament (NfL), in eight different
contact sports (i.e. boxing, American football, ice hockey, soccer, mixed
martial arts, lacrosse, rugby and wrestling), matched our inclusion
criteria. In 13/18 athlete cohorts, significant NfL elevations in CSF or
serum/plasma were described, as compared to situations of non-exposure.
Most compelling evidence was present in boxers and American football
players, where marked and/or immediate exposure-related increases were
appreciable at the intra-individual level in exclusive cohorts, generally
paired with control groups who were well-described and matched for age.
Findings in others sports were less suitable to draw conclusion upon. No
studies were encountered that have investigated the relationship with the
targeted clinical endpoints.  Conclusion: Nfl release
can be seen, as a potential marker of neuronal brain damage, in
participants of physical contact sports, particularly boxing and American
football. The exact significance regarding the risk for future clinical
impairment remains to be elucidated.