Serum Neurofilament Light Chain Concentration Correlates with Infarct Volume but Not Prognosis in Acute Ischemic Stroke

Abstract

Background and purpose: We studied serum neurofilaments diagnostic value in patients with acute ischemic stroke (AIS) or TIA and evaluated any correlation with symptom severity, cerebral infarction volume, aetiology, and clinical outcome.

Methods: One hundred and thirty-six patients (101 with AIS, and 35 with TIA) were included. Acute-phase serum neurofilament light chain (sNfL) was analyzed with a novel ultrasensitive single molecule array (Simoa). Cerebral infarction volume was measured from brain computed tomography in the subacute phase (>2 days). Stroke aetiology was defined by trial of ORG 10172 in acute stroke treatment classification, severity by National Institute of Health stroke scale (NIHSS) and the degree of disability by the Modified Rankin Scale (mRS) after 90 days.

Results: sNfL was markedly higher in patients with AIS (89.5 pg/mL [IQR: 44.7-195.3]) than with TIA (25.2 pg/mL [IQR: 14.6-48.0]), P= <.001), also after adjusting for age, NIHSS, and stroke volume (P= .003). In receiver operating characteristic analysis, sNfL concentration greater than or equal to 49 pg/mL proved to be the best cut-off value to differentiate between patients with stroke and those with TIA (sensitivity of 73% and specificity of 80%). sNfL concentration significantly correlated with cerebral infarction volume (r = .413, P= <.001), this association remained significant after adjusting for established predictors (P= .019). Patients with AIS due to cardioembolism or large artery atherosclerosis had the highest sNfL concentrations. NIHSS on admission (r = .343, P = <.001) and mRS scores after 3 months (r = .306, P = .004) correlated with sNfL concentration, however functional outcome 3 months after stroke was not associated with sNfL after adjusting for potential confounders.

Conclusions: Cases with stroke were distinguishable from those with TIA following the determination of sNfL in the blood samples. The presence and amount of axonal damage estimated by sNfL correlated with the final cerebral infarction volume but was not predictive of degree of disability.

Keywords: Ischemic; Simoa; TIA; biomarker; light; neurofilament; stroke.