Research ArticleStroke

Plasma neurofilament light predicts mortality in patients with stroke

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Science Translational Medicine  11 Nov 2020:
Vol. 12, Issue 569, eaay1913
DOI: 10.1126/scitranslmed.aay1913

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Circulating marker of brain damage

The outcome of a stroke varies greatly between patients from temporary mild symptoms to permanent disability and death. Clinical scale for measuring disease severity shows poor correlation with brain tissue damage. Identification of better markers of tissue damage could improve the ability to predict outcome and promote the development of better therapies. Now, Gendron et al. showed that the expression of circulating neurofilament light (NFL) was increased in multiple cohorts of patients with stroke compared to controls and correlated with brain tissue damage. In addition, blood concentration of NFL correlated with functional outcome and mortality. The results suggest that blood NFL might be used as prognostic marker after stroke.


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.

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