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神经元特异性烯醇化酶与急性细菌性脑膜炎患者脑代谢受损相关;一项观察性队列研究。

Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study.

作者信息

Bartek Jiri, Thelin Eric Peter, Ghatan Per Hamid, Glimaker Martin, Bellander Bo-Michael

机构信息

Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

出版信息

PLoS One. 2016 Mar 28;11(3):e0152268. doi: 10.1371/journal.pone.0152268. eCollection 2016.

Abstract

INTRODUCTION

Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM.

METHODS

From a prior study on patients (n = 52) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12-55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied.

RESULTS

The included patients had a mean GCS of 8 (range, 3-10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11) and those with a metabolic crisis (Glucose <0.8 mmol/L, LPR >25, p = 0.09). No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0-24 h) and day 3 (48-72 h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found.

CONCLUSION

In this observational cohort study, we were able to show that cerebral metabolism is frequently affected in patients with ABM. Furthermore, patients with high LPR (LPR>40) had significantly higher levels of NSE, suggesting ongoing deterioration in compromised cerebral tissue. However, the potential clinical impact of MD and biomarker monitoring in ABM patients will need to be further elaborated in larger clinical trials.

摘要

引言

对于意识水平下降的急性细菌性脑膜炎(ABM)患者,颅内压(ICP)引导治疗已被证明能改善临床预后。通过使用颅内微透析(MD)监测脑代谢,并结合指示脑组织损伤的生物标志物血清样本,如S100B和神经元特异性烯醇化酶(NSE),可能会提供更多信息。本研究的目的是评估ABM患者血清中的生物标志物和MD参数。

方法

从先前一项对确诊为ABM且意识受损(格拉斯哥昏迷评分[GCS]≤9,或GCS = 10且腰椎穿刺初压>400 mmHg2O)的患者(n = 52)的研究中,选取接受脑内MD和生物标志物监测的患者亚组(n = 21)纳入本研究。所有患者在神经重症监护病房(NICU)接受颅内压(ICP)引导治疗。入院时及每12小时采集血清生物标志物。分析MD参数葡萄糖、乳酸、丙酮酸和甘油。出院后12 - 55个月评估预后。应用曼 - 惠特尼U检验和威尔科克森配对符号秩检验。

结果

纳入患者入院时平均GCS为8(范围3 - ),62%(n = 13/21)的患者观察到颅内压升高(>20 mmHg)。乳酸与丙酮酸比值(LPR)>40的患者(n = 9/21,43%)血清NSE峰值水平显著更高(p = 0.03),甘油水平高(>500 μmol/L,p = 0.11)的患者和发生代谢危机(葡萄糖<0.8 mmol/L,LPR >25,p = 0.09)的患者也有类似但不显著的观察结果。未发现血清S100B与MD参数之间存在关联。此外,入住NICU后第1天(0 - 24小时)至第3天(48 - 72小时),MD葡萄糖水平中位数显著下降(p = 0.0001)。未发现MD参数或生物标志物与预后之间存在相关性。

结论

在这项观察性队列研究中,我们能够表明ABM患者的脑代谢经常受到影响。此外,LPR高(LPR>40)的患者NSE水平显著更高,表明受损脑组织持续恶化。然而,MD和生物标志物监测对ABM患者的潜在临床影响需要在更大规模的临床试验中进一步阐述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9127/4809596/03440831d14b/pone.0152268.g001.jpg

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