Neurofilament Light as a Biomarker in Traumatic Brain Injury

Neurology
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Shahim P, Politis A, van der Merwe A, Moore B, Chou YY, Pham DL, Butman JA, Diaz-Arrastia R, Gill JM, Brody DL, Zetterberg H, Blennow K and Chan L.

Neurology. 2020 Jul 8;10.1212/WNL.0000000000009983

DOI: 10.1212/WNL.0000000000009983

Abstract

Objective: To determine if serum neurofilament light (NfL) correlates with cerebrospinal fluid (CSF) NfL, 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 2011-2019. The Swedish cohort included 45 hockey players with acute concussion (AC) sampled at six days, 31 repetitive concussion (RC) with persistent post-concussive symptoms (PCS) assessed with paired CSF and serum (median, 1.3 years after concussion), 28 preseason controls, and 14 non-athletic 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 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 were 0.97. In the clinic-based cohort, NfL at enrolment distinguished patients with mild vs moderate vs severe TBI (p<0.001 and p=0.048). Serum NfL decreased over the course of five 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.

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