Onatsu Juha, Vanninen Ritva, Jäkälä Pekka, Mustonen Pirjo, Pulkki Kari, Korhonen Miika, Hedman Marja, Zetterberg Henrik, Blennow Kaj, Höglund Kina, Herukka Sanna-Kaisa, Taina Mikko
Department of Neurology, NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland; Department of Clinical Radiology, University of Eastern Finland, Kuopio Finland.
J Stroke Cerebrovasc Dis. 2019 Aug;28(8):2242-2249. doi: 10.1016/j.jstrokecerebrovasdis.2019.05.008. Epub 2019 May 28.
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.
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.
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.
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.
我们研究了血清神经丝蛋白在急性缺血性卒中（AIS）或短暂性脑缺血发作（TIA）患者中的诊断价值，并评估了其与症状严重程度、脑梗死体积、病因及临床结局的相关性。
纳入136例患者（101例AIS患者和35例TIA患者）。采用新型超灵敏单分子阵列（Simoa）分析急性期血清神经丝轻链（sNfL）。在亚急性期（>2天）通过脑部计算机断层扫描测量脑梗死体积。根据急性卒中治疗分类中ORG 10172试验确定卒中病因，根据美国国立卫生研究院卒中量表（NIHSS）评估严重程度，根据改良Rankin量表（mRS）评估90天后的残疾程度。
AIS患者的sNfL水平（89.5 pg/mL [四分位间距：44.7 - 195.3]）显著高于TIA患者（25.2 pg/mL [四分位间距：14.6 - 48.0]），P <.001），在调整年龄、NIHSS和卒中体积后仍有显著差异（P =.003）。在受试者工作特征分析中，sNfL浓度大于或等于49 pg/mL被证明是区分卒中患者和TIA患者的最佳临界值（敏感性为73%，特异性为80%）。sNfL浓度与脑梗死体积显著相关（r = 0.413，P <.001），在调整既定预测因素后这种关联仍然显著（P =.019）。心源性栓塞或大动脉粥样硬化所致AIS患者的sNfL浓度最高。入院时的NIHSS（r = 0.343，P <.001）和3个月后的mRS评分（r = 0.306，P =.004）与sNfL浓度相关，然而在调整潜在混杂因素后，卒中后3个月的功能结局与sNfL无关。
通过检测血样中的sNfL可区分卒中患者和TIA患者。sNfL评估的轴突损伤的存在和程度与最终脑梗死体积相关，但不能预测残疾程度。
