Serum neurofilament light as diagnostic biomarker for acute cerebral ischemia: a promising tool

The search for serum markers to detect acute and chronic cerebral damage has become of vital importance in the clinical diagnosis and monitoring of neurological diseases. In the past few years many studies have found an elevated serum neurofilament light chain (sNfL) level in the cerebrospinal fluid in patients with chronic neurodegenerative diseases [1–3], and the concentration of this marker in the serum and cerebrospinal fluid has been found to be associated with acute nerve damage, particularly in the central nervous system [4]. However, data about such biomarker findings in patients suffering from acute cerebral ischemia are lacking. One study showed an association between sNfL and stroke severity in patients diagnosed with cervical artery dissection [5]. In this issue of European Journal of Neurology, De Marchis et al. [6] present a prospective study of sNfL in patients with acute cerebrovascular ischemia. The sNfL level was found to be increased in patients who suffered an acute cerebrovascular event compared with healthy controls (15.0 vs. 2.5 pg/mL; P < 0.001). A comparison between stroke and transient ischaemic attack also showed a significant difference, as the sNfL level in stroke patients was higher than in transient ischaemic attack patients (16 vs. 9 pg/mL; P < 0.001). The sNfL level in the stroke patients was strongly associated with stroke severity measured on the National Institutes of Health Stroke Scale at admission. In stroke patients who received intravenous thrombolysis, there was an increase in sNfL from admission to 24 h after stroke. Patients with poor functional outcomes within 3 months after stroke showed higher sNfL concentration at admission than those with good outcomes, although this finding was not supported by the multivariate analysis. Furthermore, no association was found between sNfL and the size of the cerebral infarction. The study by De Marchis et al. [6] has several strengths: prospective design, large cohort and wellassessment as part of the clinical daily routine. Despite these strengths, one limitation that should be highlighted is that the sNfL levels were measured by an electrochemiluminescence-based immunoassay, which is less sensitive than the single-molecule array (Simoa) [7]. This raises an important question as to whether the method used to measure the sNfL levels may explain the differences of sNfL levels in healthy controls found in a previous study [4]. In conclusion, sNfL as a biomarker could play an additional role in diagnosing patients suffering from acute cerebrovascular events in the future. Magnetic resonance brain imaging is a very sensitive tool for the clinical diagnosis of cerebral ischemia, but the limited availability of magnetic resonance imaging and its several contraindications have resulted in the search for new diagnostic and predictive tools in the management of patients suffering from acute cerebrovascular events. Further studies are needed to confirm these findings and also to optimize the methods used for the measurement of this proposed biomarker as part of the clinical routine.