Neurofilament light as a biomarker in traumatic brain injury

Objective: To determine whether serum neurofilament light (NfL)
correlates with CSF NfL, traumatic brain injury (TBI) diagnosis, injury
severity, brain volume, and diffusion tensor imaging (DTI) estimates of
traumatic axonal injury (TAI). Methods: Participants were
prospectively enrolled in Sweden and the United States between 2011 and
2019. The Swedish cohort included 45 hockey players with acute concussion
sampled at 6 days, 31 with repetitive concussion with persistent
postconcussive symptoms (PCS) assessed with paired CSF and serum (median
1.3 years after concussion), 28 preseason controls, and 14 nonathletic
controls. Our second cohort included 230 clinic-based participants (162
with TBI and 68 controls). Patients with TBI also underwent serum,
functional outcome, and imaging assessments at 30 (n=30), 90 (n=48), and
180 (n=59) days and 1 (n=84), 2 (n=57), 3 (n= 46), 4 (n = 38), and 5 (n =
29) years after injury. Results: In athletes with paired
specimens, CSF NfL and serum NfL were correlated (r =
0.71, p < 0.0001). CSF and serum NfL
distinguished players with PCS >1 year from PCS ≤1 year
(area under the receiver operating characteristic curve [AUROC] 0.81 and
0.80). The AUROC for PCS >1 year vs preseason controls was 0.97. In
the clinic-based cohort, NfL at enrollment distinguished patients with
mild from those with moderate and severe TBI (p < 0.001
and p = 0.048). Serum NfL decreased over the course of 5
years (ß = −0.09 log pg/mL, p < 0.0001)
but remained significantly elevated compared to controls. Serum NfL
correlated with measures of functional outcome, MRI brain atrophy, and DTI
estimates of TAI. Conclusions: Serum NfL shows promise as a
biomarker for acute and repetitive sports-related concussion and patients
with subacute and chronic TBI. Classification of Evidence: This
study provides Class III evidence that increased concentrations of NfL
distinguish patients with TBI from controls.