脑脊髓液和静脉生物标志物对分流反应性特发性正常压力脑积水的诊断价值：系统评价和荟萃分析。
Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.
机构信息
Faculty of Medicine, Imperial College London, London, UK.
Department of Neurosurgery, Imperial College Healthcare NHS Trust, London, UK.
出版信息
Acta Neurochir (Wien). 2022 Jul;164(7):1719-1746. doi: 10.1007/s00701-022-05154-5. Epub 2022 Mar 1.
BACKGROUND
Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.
OBJECTIVE
To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately.
METHODS
Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.
RESULTS
The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1-42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1-42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (- 0.55 SMD, p = 0.04) and Total-Tau (- 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1-42 (- 0.26 SMD, p = 0.55) or the other included biomarkers.
CONCLUSION
This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1-42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.
背景
特发性正常压力脑积水（iNPH）是一种涉及脑脊液（CSF）稳态紊乱的神经退行性疾病和痴呆亚型。通过分流手术进行 CSF 引流后，iNPH 患者的临床状况可能会得到改善，但预测哪些患者对分流有反应仍然是一个挑战。有人提出，CSF 和血液生物标志物可用于预测 iNPH 中的分流反应。
目的
进行系统评价和荟萃分析，以确定哪些 CSF 和静脉生物标志物最能准确预测分流反应性 iNPH。
方法
使用以下数据库搜索研究 CSF 和静脉生物标志物用于预测分流反应的原始研究：Embase、MEDLINE、Scopus、PubMed、Google Scholar 和 JSTOR。使用 ROBINS-I 工具评估纳入研究，并使用单变量荟萃分析评估合格研究。
结果
该研究纳入了 13 项研究；7 项研究探讨了腰椎 CSF 中淀粉样蛋白-β 1-42 的水平，9 项研究探讨了 CSF 中总 Tau 的水平，6 项研究探讨了 CSF 中磷酸化 Tau 的水平，7 项研究探讨了其他生物标志物、蛋白质组学和基因分型。对 6 项合格研究进行的淀粉样蛋白-β 1-42、总 Tau 和磷酸化 Tau 的荟萃分析表明，分流无反应性 iNPH 的腰椎 CSF 磷酸化 Tau（-0.55 SMD，p=0.04）和总 Tau（-0.50 SMD，p=0.02）水平显著升高，但在分流反应性与无反应性 iNPH 之间，淀粉样蛋白-β 1-42（-0.26 SMD，p=0.55）或其他纳入的生物标志物之间没有差异。
结论
本荟萃分析发现，与分流反应性 iNPH 相比，分流无反应性 iNPH 的腰椎 CSF 中磷酸化 Tau 和总 Tau 水平显著升高。其他生物标志物，包括淀粉样蛋白-β 1-42，并未显著区分分流反应性与分流无反应性 iNPH。需要更多关于 Tau 蛋白的研究，以不同的临界值来检查其敏感性和特异性，从而对 Tau 蛋白的诊断效率进行稳健分析。
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