Neurofilament light chain in patients with a concussion or head impacts: a systematic review and meta-analysis

Purpose: Traumatic brain injury is one of the leading causes of disability worldwide. Mild traumatic brain injury (TBI) is the most common and benign form of TBI, usually referred to by the medical term "concussion". The purpose of our systematic review and meta-analysis was to explore the role of serum and CSF neurofilament light chain (NfL) as a potential biomarker in concussion.

Methods: We systematically searched PubMed, Web of Science, and Cochrane databases using specific keywords. As the primary outcome, we assessed CSF or serum NfL levels in patients with concussion and head impacts versus controls. The role of NfL in patients with concussion and head impacts compared to healthy controls was also assessed, as well as in sports-related and military-related conditions.

Results: From the initial 617 identified studies, we included 24 studies in our qualitative analysis and 14 studies in our meta-analysis. We found a statistically significant increase of serum NfL in patients suffering from a concussion or head impacts compared to controls (p = 0.0023), highlighting its potential role as a biomarker. From our sub-group analyses, sports-related concussion and mild TBI were mostly correlated with increased serum NfL values. Compared to controls, sports-related concussion was significantly associated with higher NfL levels (p = 0.0015), while no association was noted in patients suffering from head impacts or military-related TBI.

Conclusion: Serum NfL levels are higher in all patients suffering from concussion compared to healthy controls. The sports-related concussion was specifically associated with higher levels of NfL. Further studies exploring the use of NfL as a diagnostic and prognostic biomarker in mild TBI and head impacts are needed.