Role of Neurofilament Light Chain as a Diagnostic Tool and Predictor of Outcome of Acute Ischemic Stroke.

Ischemic stroke is the second leading cause of death and disability with symptoms ranging from complete remission within 24 h (transient ischemic attack, TIA) to lasting disability in the form of cognitive dysfunction, physical disability, and complete dependency on others. The currently available acute treatments of intravenous administration of tissue plasminogen activator (2) and mechanical thrombectomy are associated with rare but severe side effects such as hemorrhage of the brain and body. Because these treatments require rapid initiation to be effective, some patients may be exposed to side effects without benefiting from the treatment. We need, therefore, to identify biomarkers that can predict functional outcome, especially in the early phases, and improve our understanding of the pathophysiological mechanisms underlying tissue damage following a stroke to develop new advanced therapeutic strategies.

When brain damage occurs, neuronal injury and disruption of axonal membranes lead to the release of cytoskeleton proteins, such as neurofilaments (NFs), into the interstitial fluid and eventually into the cerebrospinal fluid (CSF) and blood. NFs are highly specific structural, neuronal cytoskeletal proteins that consist of four NF subunits: NF light (NF-L), NF medium (NFM), and NF heavy (NF-H) chains, and alpha-internexin.

NF-L has been studied as a potential CSF and circulation biomarker for a wide range of neurological disorders (3), including cerebral small vessel disease (4) and subacute ischemic stroke.

The inflammatory process that ensues after a stroke destabilizes the blood-brain barrier (BBB) and contributes to neuro-axonal damage, thereby increasing the release of NFs and glial and inflammatory markers into the CSF and blood.

Ischemic stroke has recently been shown to cause persistent elevations in serum NF-L that correlated with infarct volumes and recurrent ischemic lesions.