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脑脊液中的急性相神经丝轻链和神经胶质纤维酸性蛋白可预测严重创伤性脑损伤后的长期预后。

Acute-Phase Neurofilament Light and Glial Fibrillary Acidic Proteins in Cerebrospinal Fluid Predict Long-Term Outcome After Severe Traumatic Brain Injury.

机构信息

Department of Anesthesiology and Intensive Care Medicine, Institution of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

出版信息

Neurocrit Care. 2024 Dec;41(3):813-827. doi: 10.1007/s12028-024-01998-0. Epub 2024 May 20.

Abstract

BACKGROUND

This study investigated trajectory profiles and the association of concentrations of the biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ventricular cerebrospinal fluid (CSF) with clinical outcome at 1 year and 10-15 years after a severe traumatic brain injury (sTBI).

METHODS

This study included patients with sTBI at the Neurointensive Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The injury was regarded as severe if patients had a Glasgow Coma Scale ≤ 8 corresponding to Reaction Level Scale ≥ 4. CSF was collected from a ventricular catheter during a 2-week period. Concentrations of NfL and GFAP in CSF were analyzed with enzyme-linked immunosorbent assay. The Glasgow Outcome Scale (GOS) was used to assess the 1-year and 10-15-year outcomes. After adjustment for age and previous neurological diseases, logistic regression was performed for the outcomes GOS 1 (dead) or GOS 2-5 (alive) and GOS 1-3 (poor) or GOS 4-5 (good) versus the independent continuous variables (NfL and GFAP).

RESULTS

Fifty-three patients with sTBI were investigated; forty-seven adults are presented in the article, and six children (aged 7-18 years) are described in Supplement 1. The CSF concentrations of NfL gradually increased over 2 weeks post trauma, whereas GFAP concentrations peaked on days 3-4. Increasing NfL and GFAP CSF concentrations increased the odds of GOS 1-3 outcome 1 year after trauma (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80, p = 0.025; and OR 1.61, 95% CI 1.09-2.37, p = 0.016, respectively). Similarly, increasing CSF concentrations of NfL and GFAP increased the odds for GOS 1-3 outcome 10-15 years after trauma (OR 2.04, 95% CI 1.05-3.96, p = 0.035; and OR 1.60, 95% CI 1.02-2.00, p = 0.040).

CONCLUSIONS

This study shows that initial high concentrations of NfL and GFAP in CSF are both associated with higher odds for GOS 1-3 outcome 1 year and 10-15 years after an sTBI, implicating its potential usage as a prognostic marker in the future.

摘要

背景

本研究旨在探讨神经丝轻链(NfL)和胶质纤维酸性蛋白(GFAP)在创伤性脑损伤(TBI)后 1 年和 10-15 年的浓度与临床预后的关系,并分析脑脊液(CSF)中的轨迹特征。

方法

本研究纳入了瑞典哥德堡萨尔格伦斯卡大学医院神经重症监护病房的 TBI 患者。格拉斯哥昏迷量表评分≤8 分(反应水平评分≥4 分)的患者被视为严重 TBI 患者。在 2 周的时间内,通过脑室内导管采集 CSF。采用酶联免疫吸附试验分析 CSF 中 NfL 和 GFAP 的浓度。格拉斯哥预后量表(GOS)用于评估 1 年和 10-15 年的预后。在调整年龄和既往神经系统疾病后,采用逻辑回归分析 GOS 1(死亡)或 GOS 2-5(存活)和 GOS 1-3(不良)或 GOS 4-5(良好)与独立连续变量(NfL 和 GFAP)之间的关系。

结果

本研究共纳入 53 例 TBI 患者,其中 47 例为成人,6 例为儿童(7-18 岁)。研究结果显示,TBI 后 2 周内 CSF 中 NfL 浓度逐渐升高,而 GFAP 浓度在第 3-4 天达到峰值。NfL 和 GFAP 浓度升高均增加了创伤后 1 年 GOS 1-3 结局的可能性(比值比 [OR] 1.73,95%置信区间 [CI] 1.07-2.80,p=0.025;OR 1.61,95%CI 1.09-2.37,p=0.016)。同样,NfL 和 GFAP 浓度升高也增加了创伤后 10-15 年 GOS 1-3 结局的可能性(OR 2.04,95%CI 1.05-3.96,p=0.035;OR 1.60,95%CI 1.02-2.00,p=0.040)。

结论

本研究表明,TBI 后初始 CSF 中 NfL 和 GFAP 浓度升高均与 1 年和 10-15 年 GOS 1-3 结局的可能性增加相关,提示其可能作为未来的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de84/11599393/0c355bd3f51a/12028_2024_1998_Fig1_HTML.jpg

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