Neurofilament Light Chain (NfL) in Blood-A Biomarker Predicting Unfavourable Outcome in the Acute Phase and Improvement in the Late Phase after Stroke.

Milos Pekny,Ulrika Wilhelmsson,Marcela Pekna,Turgut Tatlisumak,Anna Stokowska,Katarina Jood

doi:10.3390/cells10061537

Abstract

Increased sensitivity of methods assessing the levels of neurofilament light chain (NfL), a neuron-specific intermediate filament protein, in human plasma or serum, has in recent years led to a number of studies addressing the utility of monitoring NfL in the blood of stroke patients. In this review, we discuss that elevated blood NfL levels after stroke may reflect several different neurobiological processes. In the acute and post-acute phase after stroke, high blood levels of NfL are associated with poor clinical outcome, and later on, the blood levels of NfL positively correlate with secondary neurodegeneration as assessed by MRI. Interestingly, increased blood levels of NfL in individuals who survived stroke for more than 10 months were shown to predict functional improvement in the late phase after stroke. Whereas in the acute phase after stroke the injured axons are assumed to be the main source of blood NfL, synaptic turnover and secondary neurodegeneration could be major contributors to blood NfL levels in the late phase after stroke. Elevated blood NfL levels after stroke should therefore be interpreted with caution. More studies addressing the clinical utility of blood NfL assessment in stroke patients are needed before the inclusion of NfL in the clinical workout as a useful biomarker in both the acute and the chronic phase after stroke.

Highlights

Stroke is the second most common cause of death globally [1,2]
The blood levels of neurofilament light chain (NfL) determined in the acute phase after stroke have been shown to be of prognostic value: in the first 3 months after ischemic stroke, high blood NfL levels correlate with unfavourable clinical outcome, both short-term and long-term [24,25,26]
In contrast to the negative findings reported in the abovementioned longitudinal study on the value of blood NfL for the prediction of cognitive impairment in small-vessel disease patients [28], the study by Stokowska et al found that elevated blood NfL levels were a positive predictor of cognitive improvement, but only in the subgroup of individuals who received rhythm- and music-based therapy, a multimodal neurorehabilitative intervention which predominantly targets the cognitive domain [11] (Figure 1C)

Summary

Introduction

Stroke is the second most common cause of death globally [1,2]. One in six individuals will get a stroke during their lifetime, and in 10% of these, stroke will be the cause of death [1,2]. In the acute phase after ischemic stroke, the blood levels of NfL were demonstrated to positively correlate both with the volume of the infarct [24,27] and with stroke-induced neurological deficit [26,27]. The blood levels of NfL determined in the acute phase after stroke have been shown to be of prognostic value: in the first 3 months after ischemic stroke, high blood NfL levels correlate with unfavourable clinical outcome, both short-term and long-term [24,25,26]. Cells 2021, 10, 1537 with lower blood NfL levels, patients with higher levels of NfL in blood samples obtained within the first 7 days after the ischemic stroke event had a 1.71-time higher risk of poor functional outcome during follow-up 3–6 months later [29]. In the acute stage after stroke, blood NfL levels reflect the extent of ischemic injury and are predictive of unfavourable outcome, in particular during the first months

Blood NfL as a Biomarker of Post-Stroke Secondary Neurodegeneration

Findings

The Non-Axonal Functions of NfL and the Aspect of Time after Stroke