TY - JOUR
T1 - Plasma neurofilament light predicts mortality in patients with stroke
AU - Gendron, Tania F.
AU - Badi, Mohammed K.
AU - Heckman, Michael G.
AU - Jansen-West, Karen R.
AU - Vilanilam, George K.
AU - Johnson, Patrick W.
AU - Burch, Alexander R.
AU - Walton, Ronald L.
AU - Ross, Owen A.
AU - Brott, Thomas G.
AU - Miller, Timothy M.
AU - Berry, James D.
AU - Nicholson, Katharine A.
AU - Wszolek, Zbigniew K.
AU - Oskarsson, Björn E.
AU - Sheth, Kevin N.
AU - Sansing, Lauren H.
AU - Falcone, Guido J.
AU - Cucchiara, Brett L.
AU - Meschia, James F.
AU - Petrucelli, Leonard
N1 - Funding Information:
This work was supported by the NIH (R35NS097273 to L.P., P01NS084974 to L.P., P01NS099114 to T.F.G. and L.P., K76AG059992 to G.J.F., R03NS112859 to G.J.F. and K.N.S., P30AG021342 to G.J.F., R01NS110721 to K.N.S., R01NS075209 to K.N.S., U01NS113445 to K.N.S., U01NS106513 to K.N.S., R01NR01833 to K.N.S., U24NS107215 to K.N.S., and U24NS107136 to K.N.S.), the Earl & Nyda Swanson Neurosciences Research Fund to J.F.M., the Harley N and Rebecca N Hotchkiss Endowed Fund in Neuroscience Research, Honoring Ken and Marietta to J.F.M., the Donald G and Jodi P Heeringa Family, and the Haworth Family Professorship in Neurodegenerative Diseases funds to Z.K.W. The Mayo Clinic Florida Familial Cerebrovascular Diseases Registry received funds from the Mayo Foundation for Medical Education and Research.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
PY - 2020/11/11
Y1 - 2020/11/11
N2 - Given the heterogeneity of stroke brain injury, there is a clear need for a biomarker that determines the degree of neuroaxonal injury across stroke types. We evaluated whether blood neurofilament light (NFL) would fulfill this purpose for patients with acute cerebral infarction (ACI; N = 227), aneurysmal subarachnoid hemorrhage (aSAH; N = 58), or nontraumatic intracerebral hemorrhage (ICH; N = 29). We additionally validated our findings in two independent cohorts of patients with ICH (N = 96 and N = 54) given the scarcity of blood biomarker studies for this deadliest stroke type. Compared to healthy individuals (N = 79 and N = 48 for the discovery and validation cohorts, respectively), NFL was higher for all stroke types. NFL associated with radiographic markers of brain tissue damage. It correlated with the extent of early ischemic injury in patients with ACI, hemorrhage severity in patients with aSAH, and intracranial hemorrhage volume in patients with ICH. In all patients, NFL independently correlated with scores from the NIH Stroke Scale, the modified Rankin Scale, and the Mini-Mental State Examination at blood draw, which respectively assess neurological, functional, and cognitive status. Furthermore, higher NFL concentrations independently associated with 3- or 6-month functional disability and higher all-cause mortality. These data support NFL as a uniform method to estimate neuroaxonal injury and forecast mortality regardless of stroke mechanism. As a prognostic biomarker, blood NFL has the potential to assist with planning supportive and rehabilitation services and improving clinical trial efficiency for stroke therapeutics and devices.
AB - Given the heterogeneity of stroke brain injury, there is a clear need for a biomarker that determines the degree of neuroaxonal injury across stroke types. We evaluated whether blood neurofilament light (NFL) would fulfill this purpose for patients with acute cerebral infarction (ACI; N = 227), aneurysmal subarachnoid hemorrhage (aSAH; N = 58), or nontraumatic intracerebral hemorrhage (ICH; N = 29). We additionally validated our findings in two independent cohorts of patients with ICH (N = 96 and N = 54) given the scarcity of blood biomarker studies for this deadliest stroke type. Compared to healthy individuals (N = 79 and N = 48 for the discovery and validation cohorts, respectively), NFL was higher for all stroke types. NFL associated with radiographic markers of brain tissue damage. It correlated with the extent of early ischemic injury in patients with ACI, hemorrhage severity in patients with aSAH, and intracranial hemorrhage volume in patients with ICH. In all patients, NFL independently correlated with scores from the NIH Stroke Scale, the modified Rankin Scale, and the Mini-Mental State Examination at blood draw, which respectively assess neurological, functional, and cognitive status. Furthermore, higher NFL concentrations independently associated with 3- or 6-month functional disability and higher all-cause mortality. These data support NFL as a uniform method to estimate neuroaxonal injury and forecast mortality regardless of stroke mechanism. As a prognostic biomarker, blood NFL has the potential to assist with planning supportive and rehabilitation services and improving clinical trial efficiency for stroke therapeutics and devices.
UR - http://www.scopus.com/inward/record.url?scp=85096081167&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aay1913
DO - 10.1126/scitranslmed.aay1913
M3 - Article
C2 - 33177179
AN - SCOPUS:85096081167
SN - 1946-6234
VL - 12
JO - Science translational medicine
JF - Science translational medicine
IS - 569
M1 - eaay1913
ER -