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肠道病毒引起的中枢神经系统感染患者的生物标志物和基因型。

Biomarkers and genotypes in patients with Central nervous system infection caused by enterovirus.

机构信息

Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.

Department of Infectious diseases, Västra Götaland Region, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Infect Dis (Lond). 2024 Sep;56(9):722-731. doi: 10.1080/23744235.2024.2345712. Epub 2024 May 17.

Abstract

PURPOSE

Enteroviruses (EV) comprises many different types and are the most common cause of aseptic meningitis. How the virus affects the brain including potential differences between types are largely unknown. Measuring biomarkers in CSF is a tool to estimate brain damage caused by CNS infections.

METHODS

A retrospective study was performed in samples from 38 patients with acute neurological manifestations and positive CSF-EV RNA ( = 37) or serum-IgM ( = 1). The EV in 17 samples were typed by sequencing. The biomarkers neurofilament light (NFL), glial fibrillary acidic protein (GFAP), S-100B protein, amyloid-β (Aβ) 40 and Aβ42, total-tau (T-tau) and phosphorylated tau (P-tau) were measured and compared with data derived from a control group ( = 19).

RESULTS

There were no increased levels of GFAP ( ≤ 0.1) nor NFL ( ≤ 0.1) in the CSF of patients with EV meningitis ( = 38) compared with controls. However, we found decreased levels of Aβ42 ( < 0.001), Aβ40 ( < 0.001), T-tau ( ≥ 0.01), P-tau ( ≤ 0.001) and S-100B ( ≤ 0.001). E30 ( = 9) and CVB5 ( = 6) were the most frequent EV-types identified, but no differences in biomarker levels or other clinical parameters were found between the infecting virus type. Seven patients who were followed for longer than one month reported remaining cognitive impairment, although no correlations with biomarker concentrations were observed.

CONCLUSION

There are no indication of neuronal or astrocyte damage in patients with EV meningitis. Yet, decreased concentrations of Aβ40, Aβ42, P-tau and T-tau were shown, a finding of unknown importance. Cognitive impairment after acute disease occurs, but with only a limited number of patients analysed, no conclusion can be drawn concerning any association with biomarker levels or EV types.

摘要

目的

肠道病毒(EV)包含许多不同类型,是无菌性脑膜炎的最常见原因。病毒如何影响大脑,包括不同类型之间的潜在差异,在很大程度上尚不清楚。测量脑脊液中的生物标志物是一种评估中枢神经系统感染引起的脑损伤的工具。

方法

对 38 例急性神经表现且脑脊液 EV RNA 阳性( = 37)或血清 IgM 阳性( = 1)的患者进行回顾性研究。对 17 例样本中的 EV 进行测序分型。测量并比较神经丝轻链(NFL)、胶质纤维酸性蛋白(GFAP)、S-100B 蛋白、淀粉样β肽(Aβ)40 和 Aβ42、总 tau(T-tau)和磷酸化 tau(P-tau)等生物标志物,与对照组( = 19)的数据进行比较。

结果

与对照组相比,EV 脑膜炎患者( = 38)的脑脊液中 GFAP( ≤ 0.1)和 NFL( ≤ 0.1)水平没有升高。然而,我们发现 Aβ42( < 0.001)、Aβ40( < 0.001)、T-tau( ≥ 0.01)、P-tau( ≤ 0.001)和 S-100B( ≤ 0.001)水平降低。E30( = 9)和 CVB5( = 6)是最常见的 EV 类型,但在感染病毒类型之间未发现生物标志物水平或其他临床参数的差异。7 例患者随访时间超过 1 个月,报告存在认知障碍,但未观察到与生物标志物浓度的相关性。

结论

EV 脑膜炎患者没有神经元或星形胶质细胞损伤的迹象。然而,我们发现 Aβ40、Aβ42、P-tau 和 T-tau 浓度降低,这一发现的重要性尚不清楚。急性疾病后发生认知障碍,但由于分析的患者数量有限,无法得出与生物标志物水平或 EV 类型有关的任何结论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ff/11371261/3688c4b5f63f/INFD_A_2345712_F0001_B.jpg

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