SCIENCE TRANSITIONAL MEDICINE | NOVEMBER 11, 2020

Gendron TF, Badi MK, Heckman MG, Jansen-West KR, Vilanilam GK, Johnson PW, Burch AR, Walton RL, Ross OA, Brott TG, Miller TM, Berry JD, Nicholson KA, Wszolek ZK, Oskarsson BE, Sheth KN, Sansing LH, Falcone GJ, Cucchiara BL, Meschia JF and Petrucelli L.

Sci Transl Med. 2020 Nov 11;12(569):eaay1913

DOI: 10.1126/scitranslmed.aay1913

ABSTRACT

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.