Vakrakou Aigli G, Tzartos John S, Strataki Eleni, Boufidou Fotini, Dimou Eleni, Pyrgelis Efstratios-Stylianos, Constantinides Vasilios C, Paraskevas George P, Kapaki Elisabeth
1st Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Eginition Hospital, 74, Vasilissis-Sofias-Avenue, 11528 Athens, Greece.
2nd Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Rimini 1, 12462 Athens, Greece.
Biomedicines. 2022 May 28;10(6):1262. doi: 10.3390/biomedicines10061262.
The aim of this study was to evaluate the association of neuronal damage biomarkers (neurofilament light chain (NFL) and total tau protein (T-tau)) in the CSF of patients with autoimmune encephalitis (AE) with the presence of an underlying malignancy and to determine correlations with patient characteristics. The study comprised 21 patients with encephalitis associated with antibodies against intracellular ( = 11) and surface/synaptic antigens (extracellular, = 10) and non-inflammatory disease controls ( = 10). Patients with AE associated with intracellular antigens had increased CSF-NFL ( = 0.003) but not T-tau levels compared to controls. When adjusted for age, CSF-NFL but not CSF-T-tau was higher in patients with encephalitis associated with intracellular antigens as compared to those with encephalitis associated with extracellular antigens ( = 0.032). Total tau and NFL levels were not significantly altered in patients with encephalitis associated with extracellular antigens compared to controls. NFL in the total cohort correlated with neurological signs of cerebellar dysfunction, peripheral neuropathy, presence of CV2 positivity, presence of an underlying tumor and a more detrimental clinical outcome. AE patients with abnormal MRI findings displayed higher NFL levels compared to those without, albeit with no statistical significance ( = 0.07). Using receiver operating characteristic curve analysis, CSF-NFL levels with a cut-off value of 969 pg/mL had a sensitivity and specificity of 100% and 76.19%, respectively, regarding the detection of underlying malignancies. Our findings suggest that neuronal integrity is preserved in autoimmune encephalitis associated with extracellular antigens and without the presence of tumor. However, highly increased NFL is observed in AE associated with intracellular antigens and presence of an underlying tumor. CSF-NFL could potentially be used as a diagnostic biomarker of underlying malignancies in the clinical setting of AE.
本研究旨在评估自身免疫性脑炎(AE)患者脑脊液中神经元损伤生物标志物(神经丝轻链(NFL)和总tau蛋白(T-tau))与潜在恶性肿瘤的相关性,并确定其与患者特征的相关性。该研究纳入了21例与细胞内抗体(n = 11)和表面/突触抗原抗体(细胞外,n = 10)相关的脑炎患者以及非炎性疾病对照(n = 10)。与对照组相比,与细胞内抗原相关的AE患者脑脊液NFL水平升高(P = 0.003),但T-tau水平未升高。在调整年龄后,与细胞外抗原相关的脑炎患者相比,与细胞内抗原相关的脑炎患者脑脊液NFL水平更高,而脑脊液T-tau水平无差异(P = 0.032)。与对照组相比,与细胞外抗原相关的脑炎患者总tau和NFL水平无显著变化。整个队列中的NFL与小脑功能障碍的神经体征、周围神经病变、CV2阳性的存在、潜在肿瘤的存在以及更不利的临床结局相关。MRI检查结果异常的AE患者NFL水平高于无异常者,尽管无统计学意义(P = 0.07)。使用受试者工作特征曲线分析,脑脊液NFL水平的截断值为969 pg/mL时,检测潜在恶性肿瘤的敏感性和特异性分别为100%和76.19%。我们的研究结果表明,在与细胞外抗原相关且无肿瘤的自身免疫性脑炎中,神经元完整性得以保留。然而,在与细胞内抗原相关且存在潜在肿瘤的AE中观察到NFL高度升高。在AE的临床环境中,脑脊液NFL可能用作潜在恶性肿瘤的诊断生物标志物。