The Value of the Serum Neurofilament Protein Heavy Chain as a Biomarker for Peri-operative Brain Injury After Carotid Endarterectomy

Abstract

This prospective study examined the value of serum neurofilament protein levels for detecting peri-operative brain damage following carotid endarterectomy. An ELISA was used for quantification of neurofilament protein heavy chain (NfH(SMI35)) levels from patients undergoing endarterectomy for symptomatic (n = 17) and asymptomatic high-grade internal carotid artery stenosis (n = 30). All patients underwent diffusion-weighted brain imaging before and after the procedure. NfH(SMI35) levels were significantly higher in patients with a symptomatic carotid artery stenosis (0.131 ng/ml) if compared to asymptomatic patients (0.055 ng/ml, P = 0.01). However, serum NfH(SMI35) levels were not related to signs of brain ischemia on routine brain imaging techniques. Our pilot data suggests that raised NfH(SMI35) serum levels in patients with symptomatic carotid artery disease may be a sensitive biomarker for diffuse ischemic damage to the CNS. We conclude that NfH(SMI35) failed to qualify as a biomarker for peri-operative brain injury in CEA and factors that may have compromised the validation of this biomarker are discussed and need to be taken into account for the design of further studies.

Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

“…The findings also extend the observation of reduced and disrupted NfH staining (NfH SMI31 and silver staining) in the ischaemic hemisphere in experimental focal ischaemia starting at 1-3 days post insult [18]. Indeed, NfH SMI35 was shown to be a sensitive marker and even subtle brain injury due to symptomatic carotid stenosis was associated with 2.4-fold higher NfH SMI35 serum levels compared to asymptomatic carotid stenosis [15]. Hence, it is tempting to speculate that increased serum levels of NfH SMI35 reflect the respective acute neuro-axonal damage evidenced on neuroimaging.…”

“…Quantification of NfH, S100B and GFAP Levels Serum NfH SMI35 levels were measured using an enzymelinked immunoassay, as described previously [10,15]. The mouse monoclonal antibody SMI35 (IgG) was originally purchased from Sternberger Monoclonals Inc., and is now available through Covance Research Products (Berkeley, CA, USA).…”

Levels of phosphorylated axonal neurofilament subunit H (pNfH) are increased in acute ischemic stroke

“…The elevated blood pNfH levels in stroke patients is consistent with findings in other neurological diseases, such as ALS [13], where levels are also elevated in CSF [15,32], peri-operative brain injury in carotid stenosis [19], aneurysmal subarachnoid haemorrhage [20] and experimental brain injury [17,18]. It is believed that axonal injury may affect the structural integrity of cytoskeletal components, leading to the eventual detachment of pNfH proteins.…”

“…pNfH degradation and release has been found in animal models of focal brain injury [17] and focal ischaemia in the brain [18]. Elevated blood levels of pNfH have been found after surgery in patients with symptomatic carotid artery disease [19], and in patients suffering from aneurysmal subarachnoid haemorrhage [20] and in patients with amyotrophic lateral sclerosis (ALS) [13] .…”

Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection

“…Thus, serum neurofilament levels may be considered a measure of structural brain lesion, complementary to MRI. Accordingly, in a study measuring sNfH levels, patients with symptomatic carotid stenosis had higher sNfH levels than patients with asymptomatic stenosis [15] . In our cohort, sNfL levels in patients with TIA and local symptoms ap- 226 peared similar and relatively comparable to those reported in healthy individuals by previous publications using the very same technology [6,14] .…”