Di Stefano Alessandro, Alcantarini Chiara, Atzori Cristiana, Lipani Filippo, Imperiale Daniele, Burdino Elisa, Audagnotto Sabrina, Mighetto Lorenzo, Milia Maria Grazia, Di Perri Giovanni, Calcagno Andrea
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
Unit of Neurology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy.
CNS Spectr. 2020 Jun;25(3):402-408. doi: 10.1017/S1092852919000981. Epub 2019 May 27.
Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy.
Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood-brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1-42 β-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100β).
Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100β was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aβ1-42.
This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.
中枢神经系统(CNS)可能受到多种病原体感染,导致不同的表现和结局。分析脑脊液(CSF)标志物有助于鉴别特定病情并制定合适的治疗方案。
出现相关症状和体征的患者,在接受诊断性腰椎穿刺前签署书面知情同意书后纳入研究。我们分析了脑脊液中血脑屏障通透性指标(脑脊液与血清白蛋白比值或CSAR)、炎症指标(脑脊液与血清IgG比值、新蝶呤)、淀粉样蛋白沉积指标(1-42β-淀粉样蛋白)、神经元损伤指标(总tau蛋白(T-tau)、磷酸化tau蛋白(P-tau)和14.3.3蛋白)以及星形胶质细胞损伤指标(S-100β)。
共纳入281例患者,主要感染类型为疱疹病毒性脑炎、肠道病毒性脑膜脑炎、细菌性脑膜炎(脑膜炎奈瑟菌和肺炎链球菌)以及其他病原体或不明病原体感染。将他们的脑脊液特征与HIV阴性患者以及未累及中枢神经系统的HIV阳性患者进行比较。在细菌性感染和单纯疱疹病毒(HSV)感染患者的脑脊液中发现了14.3.3蛋白,而疱疹病毒组中T-tau和新蝶呤异常升高。相反,肠道病毒性脑膜炎患者脑脊液中P-tau升高。HSV-1和HSV-2感染患者脑脊液中S-100β升高,而水痘带状疱疹病毒(VZV)感染患者脑脊液中S-100β未升高。30天死亡率出人意料地低(2.7%):死亡患者T-tau水平较高,且Aβ1-42水平显著较低。
本研究表明,中枢神经系统感染期间,神经元损伤或炎症的脑脊液生物标志物可能因病原体不同而有所差异。这些生物标志物的预后价值需要在前瞻性研究中进行评估。