Objective: To investigate whether professional athletes with post-concussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) have elevated cerebrospinal fluid (CSF) and plasma neurofilament light (NF-L) and tau as compared to controls, and whether elevated concentrations of these biomarkers are associated with persistent PCS.

Background: Recently, CSF NF-L and tau have been reported to increase following acute repetitive head trauma. However, whether these biomarkers are elevated in CSF and plasma of athletes with PCS following rcTBI is unknown.

Design/Methods: A total of 109 participants (31 professional athletes with PCS due to rcTBI, 48 concussed athletes without PCS, and 30 non-concussed athletic controls) were enrolled between September 2013 and September 2017. Athletes with PCS due to rcTBI also underwent paired CSF and plasma biomarker assessments, Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and structural MRI of the brain (median, 1.5 years since last concussion).

Results: Plasma NF-L concentrations were significantly increased in both the concussed and PCS group as compared with athletic controls. Among athletes with PCS, the highest concentrations of NF-L were observed in athletes with PCS > 1 year as compared to those with PCS < 1 year (area under the receiver-operating characteristics, 0.85). Furthermore, plasma concentrations of NF-L correlated with RPQ scores and lifetime number of concussions. In contrast, CSF and plasma concentrations of tau were not associated with injury severity or duration of PCS. Consistently, CSF NF-L correlated with corresponding plasma (r = 0.81, P < 0.001), while there was no significant correlation between CSF tau and corresponding plasma.

Conclusions: Persistent PCS due to rcTBI is associated with axonal injury, which can be monitored by measuring NF-L in plasma samples months to year after last concussion. From a clinical standpoint, incorporation of plasma NF-L in the work-up may aid in distinguishing patients at increased risk of developing persistent PCS.

Disclosure: Dr. Shahim has nothing to disclose. Dr. Tegner has nothing to disclose. Dr. Blennow has nothing to disclose. Dr. Zetterberg has nothing to disclose.