Department of Neurology, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. 1, 17475, Greifswald, Germany.
Department of Neurology With Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
J Headache Pain. 2024 Apr 2;25(1):46. doi: 10.1186/s10194-024-01757-8.
To date, migraine is diagnosed exclusively based on clinical criteria, but fluid biomarkers are desirable to gain insight into pathophysiological processes and inform clinical management. We investigated the state-dependent profile of fluid biomarkers for neuroaxonal damage and microglial activation as two potentially relevant aspects in human migraine pathophysiology.
This exploratory study included serum and cerebrospinal fluid (CSF) samples of patients with migraine during the headache phase (ictally) (n = 23), between attacks (interictally) (n = 16), and age/sex-matched controls (n = 19). Total Tau (t-Tau) protein, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured with the Neurology 4-plex kit on a Single Molecule Array SR-X Analyzer (Simoa® SR-X, Quanterix Corp., Lexington, MA). Markers of microglial activation, C-X3-C motif chemokine ligand 1 (CX3CL1) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), were assessed using an immunoassay.
Concentrations of CX3CL1 but not sTREM2 were significantly increased both ictally and interictally in CSF but not in serum in comparison to the control cohort (p = 0.039). ROC curve analysis provided an AUC of 0.699 (95% CI 0.563 to 0.813, p = 0.007). T-Tau in serum but not in CSF was significantly increased in samples from patients taken during the headache phase, but not interictally (effect size: η = 0.121, p = 0.038). ROC analysis of t-Tau protein in serum between ictal and interictal collected samples provided an AUC of 0.729 (95% CI 0.558 to 0.861, p = 0.006). The other determined biomarkers for axonal damage were not significantly different between the cohorts in either serum or CSF.
CX3CL1 in CSF is a novel potential fluid biomarker of migraine that is unrelated to the headache status. Serum t-Tau is linked to the headache phase but not interictal migraine. These data need to be confirmed in a larger hypothesis-driven prospective study.
迄今为止，偏头痛的诊断仅基于临床标准，但需要体液生物标志物来深入了解病理生理过程并为临床管理提供信息。我们研究了神经轴突损伤和小胶质细胞激活的体液生物标志物在人类偏头痛病理生理学中的状态相关特征，这两个方面可能是相关的。
本探索性研究纳入了偏头痛患者头痛发作期（发作期）（n=23）、发作间期（n=16）和年龄/性别匹配的对照组（n=19）的血清和脑脊液（CSF）样本。应用单分子阵列 SR-X 分析仪（Simoa® SR-X，Quanterix 公司，马萨诸塞州列克星敦）上的神经学 4 合 1 试剂盒测量总 Tau（t-Tau）蛋白、神经胶质纤维酸性蛋白（GFAP）、泛素羧基末端水解酶 L1（UCH-L1）和神经丝轻链（NfL）。应用免疫测定法评估小胶质细胞激活标志物 C-X3-C 基序趋化因子配体 1（CX3CL1）和可溶性髓样细胞触发受体 2（sTREM2）。
与对照组相比，CSF 中 CX3CL1 但不是 sTREM2 的浓度在发作期和发作间期均显著升高，但血清中无此变化（p=0.039）。ROC 曲线分析的 AUC 为 0.699（95%CI 0.563 至 0.813，p=0.007）。发作期患者血清中 T-Tau 但不是 CSF 中 T-Tau 明显升高，但发作间期无此变化（效应大小：η=0.121，p=0.038）。发作期和发作间期采集的血清样本 t-Tau 蛋白的 ROC 分析的 AUC 为 0.729（95%CI 0.558 至 0.861，p=0.006）。在血清或 CSF 中，其他确定的轴突损伤生物标志物在各队列之间均无显著差异。
CSF 中的 CX3CL1 是偏头痛的一种新的潜在体液生物标志物，与头痛状态无关。血清 t-Tau 与头痛期有关，但与发作间期偏头痛无关。这些数据需要在更大的假设驱动前瞻性研究中得到证实。
Zotero 插件
