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Abstract
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.
Glossary
- AC=
- acute concussion;
- AD=
- axial diffusivity;
- AUROC=
- area under the receiver operating characteristic curve;
- BBB=
- blood-brain barrier;
- CC=
- corpus callosum;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- GM=
- gray matter;
- GOS-E=
- Glasgow Outcome Scale-Extended;
- IQR=
- interquartile range;
- MD=
- mean diffusivity;
- mTBI=
- mild TBI;
- NfL=
- neurofilament light;
- PCS=
- postconcussive symptoms;
- RC=
- repetitive concussion;
- RD=
- radial diffusivity;
- RTP=
- return to play;
- TAI=
- traumatic axonal injury;
- TBI=
- traumatic brain injury;
- WM=
- white matter
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
Editorial, page 235
See page 242
- Received August 29, 2019.
- Accepted in final form January 7, 2020.
- © 2020 American Academy of Neurology
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