这项系统评价和荟萃分析(SR-MA)的目的是确定偏头痛和丛集性头痛(CH)患者的信号分子谱和血液来源的生物标志物。
目前尚无偏头痛和CH有效的生物标志物。基于生物标志物谱的血液测试已用于收集有关神经系统的信息。在原发性头痛领域尚未建立此类测试。
调查全血的病例对照和病例交叉研究,等离子体,和血清在世界范围内被鉴定。定性合成集中在9个信号分子(5-羟色胺[5-HT],降钙素基因相关肽[CGRP],内皮素-1[ET-1],神经激肽A,神经激肽B,神经肽Y,垂体腺苷酸环化酶激活肽38[PACAP-38],P物质(SP),和血管活性肠肽)以及5-HT和CGRP的定量合成(≥5个比较可用)。使用标准和3水平随机效应模型进行荟萃分析。
确定了54项符合条件的研究(87.0%的偏头痛,9.3%CH,3.7%偏头痛,和CH),包括2768名头痛患者和1165名对照。5-HT的可比波动,CGRP,在偏头痛和CH之间通常观察到血液中的ET-1,PACAP-38和SP。在一些亚组和地层中观察到了显著的发现,例如,较高的发作间和发作间5-HT静脉血水平(平均比率=1.32,95%CI:1.08;1.61;平均比率=1.23,95%CI:1.01;1.49)在女性主导病例组中,发作性偏头痛患者的发作间CGRP血液水平较高(均值比率=1.63,95%CI:1.18;2.26),和慢性偏头痛(平均比率=1.89,95%CI:1.33;2.68),在发作性偏头痛中观察到较高的CGRP血液水平(平均值=1.35,95%CI:1.09;1.68)。在大多数子群中,定量综合显示了研究之间的高度异质性,部分原因是血液采样部位,标本来源,血液样本,和性别分布。其他潜在的混杂因素是年龄,光环,学习质量,月经周期,和方法论(例如,储存温度)。
揭示了潜在的偏头痛和CH信号分子谱和生物标志物。然而,研究之间的高度异质性阻碍了有效生物标志物的鉴定,但使我们能够评估混杂因素的存在.考虑在此SR-MA中确定的潜在混杂因素可能在未来研究的实验计划中很重要。可以通过制定具体准则来纳入这一考虑。
The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients.
Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field.
Case-control and
case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models.
Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated
case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature).
Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines.