Pashtun Shahim1, Adam Politis2, Andre van der Merwe2, Brian Moore2, Yi-Yu Chou2, Dzung L Pham2, John A Butman2, Ramon Diaz-Arrastia2, Jessica M Gill2, David L Brody2, Henrik Zetterberg2, Kaj Blennow2, Leighton Chan2. 1. From the NIH (P.S., A.P., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); Center for Neuroscience and Regenerative Medicine (P.S., A.v.d.M., B.M., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); The Henry M. Jackson Foundation for the Advancement of Military Medicine (P.S., A.v.d.M., B.M., J.M.G., D.L.B.), Bethesda, MD; Department of Psychiatry and Neurochemistry (P.S., H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Uniformed Services University of the Health Sciences (D.L.B.), Bethesda, MD; Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia; UK Dementia Research Institute at UCL (H.Z.); and Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London, UK. pashtun-poh.shahim@nih.gov. 2. From the NIH (P.S., A.P., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); Center for Neuroscience and Regenerative Medicine (P.S., A.v.d.M., B.M., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); The Henry M. Jackson Foundation for the Advancement of Military Medicine (P.S., A.v.d.M., B.M., J.M.G., D.L.B.), Bethesda, MD; Department of Psychiatry and Neurochemistry (P.S., H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Uniformed Services University of the Health Sciences (D.L.B.), Bethesda, MD; Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia; UK Dementia Research Institute at UCL (H.Z.); and Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London, UK.
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.
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.
Authors: Jeffrey J Bazarian; Peter Biberthaler; Robert D Welch; Lawrence M Lewis; Pal Barzo; Viktoria Bogner-Flatz; P Gunnar Brolinson; Andras Büki; James Y Chen; Robert H Christenson; Dallas Hack; J Stephen Huff; Sandeep Johar; J Dedrick Jordan; Bernd A Leidel; Tobias Lindner; Elizabeth Ludington; David O Okonkwo; Joseph Ornato; W Frank Peacock; Kara Schmidt; Joseph A Tyndall; Arastoo Vossough; Andy S Jagoda Journal: Lancet Neurol Date: 2018-07-24 Impact factor: 44.182
Authors: Johanna Gaiottino; Niklas Norgren; Ruth Dobson; Joanne Topping; Ahuva Nissim; Andrea Malaspina; Jonathan P Bestwick; Andreas U Monsch; Axel Regeniter; Raija L Lindberg; Ludwig Kappos; David Leppert; Axel Petzold; Gavin Giovannoni; Jens Kuhle Journal: PLoS One Date: 2013-09-20 Impact factor: 3.240
Authors: Magnus Gisslén; Richard W Price; Ulf Andreasson; Niklas Norgren; Staffan Nilsson; Lars Hagberg; Dietmar Fuchs; Serena Spudich; Kaj Blennow; Henrik Zetterberg Journal: EBioMedicine Date: 2016-04-20 Impact factor: 8.143
Authors: Christina M Marion; Kryslaine L Radomski; Nathan P Cramer; Zygmunt Galdzicki; Regina C Armstrong Journal: J Neurosci Date: 2018-08-24 Impact factor: 6.167
Authors: William R McBride; Caroline E Conlan; Nicole A Barylski; Amelie C Warneryd; Randel L Swanson Journal: Curr Phys Med Rehabil Rep Date: 2022-02-26
Authors: Pashtun Shahim; Henrik Zetterberg; Joel Simrén; Nicholas J Ashton; Gina Norato; Michael Schöll; Yelverton Tegner; Ramon Diaz-Arrastia; Kaj Blennow Journal: Neurology Date: 2022-06-02 Impact factor: 11.800
Authors: David F Tate; Emily L Dennis; John T Adams; Maheen M Adamson; Heather G Belanger; Erin D Bigler; Heather C Bouchard; Alexandra L Clark; Lisa M Delano-Wood; Seth G Disner; Blessen C Eapen; Carol E Franz; Elbert Geuze; Naomi J Goodrich-Hunsaker; Kihwan Han; Jasmeet P Hayes; Sidney R Hinds; Cooper B Hodges; Elizabeth S Hovenden; Andrei Irimia; Kimbra Kenney; Inga K Koerte; William S Kremen; Harvey S Levin; Hannah M Lindsey; Rajendra A Morey; Mary R Newsome; John Ollinger; Mary Jo Pugh; Randall S Scheibel; Martha E Shenton; Danielle R Sullivan; Brian A Taylor; Maya Troyanskaya; Carmen Velez; Benjamin Sc Wade; Xin Wang; Ashley L Ware; Ross Zafonte; Paul M Thompson; Elisabeth A Wilde Journal: Brain Imaging Behav Date: 2021-01-07 Impact factor: 3.978
Authors: Simon Thebault; Ronald A Booth; Carolina A Rush; Heather MacLean; Mark S Freedman Journal: Front Neurosci Date: 2021-03-25 Impact factor: 4.677
Authors: Ulrika Sjöbom; William Hellström; Chatarina Löfqvist; Anders K Nilsson; Gerd Holmström; Ingrid Hansen Pupp; David Ley; Kaj Blennow; Henrik Zetterberg; Karin Sävman; Ann Hellström Journal: JAMA Netw Open Date: 2021-04-01
Authors: Kryshawna Beard; Zijian Yang; Margalit Haber; Miranda Flamholz; Ramon Diaz-Arrastia; Danielle Sandsmark; David F Meaney; David Issadore Journal: Brain Commun Date: 2021-07-08