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

Karolina Alsén, Marianela Patzi Churqui, Helene Norder, Karolina Rembeck, Henrik Zetterberg, K. Blennow, Fredrika Sahlgren, Anna Grahn
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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 (n = 37) or serum-IgM (n = 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 (n = 19). RESULTS There were no increased levels of GFAP (p ≤ 0.1) nor NFL (p ≤ 0.1) in the CSF of patients with EV meningitis (n = 38) compared with controls. However, we found decreased levels of Aβ42 (p < 0.001), Aβ40 (p < 0.001), T-tau (p ≥ 0.01), P-tau (p ≤ 0.001) and S-100B (p ≤ 0.001). E30 (n = 9) and CVB5 (n = 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.
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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记物和基因型。
目的脊髓灰质炎病毒(EV)有多种不同类型,是无菌性脑膜炎最常见的病因。病毒如何影响大脑,包括不同类型病毒之间的潜在差异,这些问题在很大程度上还不清楚。测量 CSF 中的生物标记物是评估中枢神经系统感染造成的脑损伤的一种工具。方法对 38 名有急性神经系统表现、CSF-EV RNA 阳性(37 人)或血清-IgM 阳性(1 人)的患者样本进行了回顾性研究。对 17 份样本中的 EV 进行了测序分型。对生物标志物神经丝光(NFL)、胶质纤维酸性蛋白(GFAP)、S-100B 蛋白、淀粉样蛋白-β(Aβ)40 和 Aβ42、总 tau(T-tau)和磷酸化 tau(P-tau)进行了测定,并与对照组(n = 19)的数据进行了比较。结果与对照组相比,EV 脑膜炎患者(n = 38)脑脊液中 GFAP(p ≤ 0.1)和 NFL(p ≤ 0.1)的水平没有增加。然而,我们发现 Aβ42 (p<0.001)、Aβ40 (p<0.001)、T-tau (p≥0.01)、P-tau (p≤0.001) 和 S-100B (p≤0.001) 水平下降。E30(9 例)和 CVB5(6 例)是最常见的 EV 类型,但不同感染病毒类型的生物标志物水平或其他临床参数并无差异。随访超过一个月的七名患者报告仍存在认知障碍,但未观察到与生物标志物浓度的相关性。然而,Aβ40、Aβ42、P-tau 和 T-tau 的浓度有所下降,这一发现的重要性尚不清楚。急性病后会出现认知障碍,但由于分析的患者人数有限,因此无法就生物标志物水平或 EV 类型之间的关联得出结论。
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Biomarkers and genotypes in patients with Central nervous system infection caused by enterovirus. Tonsillectomies are associated with an increased risk of meningococcal carriage. Sensitive and rapid identification of pathogens by droplet digital PCR in a cohort of septic patients: a prospective diagnostic study. Resurgence of Syphilis in the United States: An Assessment of Contributing Factors. Demographic Determinants of Influenza Vaccination and Infection, Brazos County, Texas, 2017.
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