Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
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DOI：
10.1212/wnl.0000000000007047
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发表时间：
2019-03-05
期刊：
影响因子：
9.9
通讯作者：
Leira, Rogelio
中科院分区：
文献类型：
--
作者：
Dominguez, Clara;Lopez, Ana;Leira, Rogelio
目的探讨铁沉积在红核（RN）、苍白球（GP）和导水管周围灰质（PAG）中作为慢性偏头痛（CM）的潜在生物标志物及其与偏头痛病理生理相关生物标志物水平的相关性。方法本研究纳入112例偏头痛患者（55例CM， 57例发作性偏头痛[EM]）和25例无头痛对照。我们使用3T MRI和NIH软件平台ImageJ分析铁沉积；我们通过ELISA分析了间歇期外周血中炎症、内皮功能障碍和血脑屏障（BBB）破坏标志物的血清水平。患者厘米结果显示体积较大的铁渣在RN EM患者相比(70.2 + / - 6.8 vs 25.5 + / - 7.3μL, p < 0.001)和控制(70.2 + / - 6.8 vs 15.1 + / - 10.8μL, p < 0.001),以及更大的铁沉积在PAG EM患者相比(360.3 + / - 6.5 vs 249.7 + / - 6.9μL, p < 0.001)和控制(360.3 + / - 6.5 vs 168.6 + / - 10.3μL, p < 0.001)。在PAG方面，EM患者和对照组之间的差异也很显著。GP无显著性差异。受试者工作特征曲线显示，铁容量的最佳阈值在RN为15 μ L（敏感性80%，特异性71%），PAG为240 μ L（敏感性93%，特异性97%）。PAG中铁渣体积与血浆可溶性肿瘤坏死因子样WEAK （r = 0.395, p = 0.005）和细胞纤维连接蛋白（r = 0.294, p = 0.040）水平升高相关。结论与EM患者和对照组相比，CM患者在RN和PAG中的铁沉积增加。PAG中的铁渣量可以正确识别CM患者，并与内皮功能障碍和血脑屏障破坏的生物标志物升高相关。
Objective To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) and its association with levels of biomarkers related to migraine pathophysiology. Methods This case-control study included 112 patients with migraine (55 CM, 57 episodic migraine [EM]) and 25 headache-free controls. We analyzed iron deposition using 3T MRI and the NIH software platform ImageJ; we analyzed serum levels of markers of inflammation, endothelial dysfunction, and blood-brain barrier (BBB) disruption by ELISA in peripheral blood during interictal periods. Results Patients with CM showed larger iron grounds volume in RN compared to patients with EM (70.2 +/- 6.8 vs 25.5 +/- 7.3 mu L, p < 0.001) and controls (70.2 +/- 6.8 vs 15.1 +/- 10.8 mu L, p < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 +/- 6.5 vs 249.7 +/- 6.9 mu L, p < 0.001) and controls (360.3 +/- 6.5 vs 168.6 +/- 10.3 mu L, p < 0.001). In PAG, differences were also significant between patients with EM and controls. No significant differences were obtained for GP. Receiver operating characteristic curves showed that the optimal threshold for iron volume was 15 mu L in RN (80% sensitivity, 71% specificity) and 240 mu L in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor-like WEAK (r = 0.395, p = 0.005) and cellular fibronectin (r = 0.294, p = 0.040). Conclusions Patients with CM showed increased iron deposition in RN and PAG compared to patients with EM and controls. Iron grounds volume in PAG identified correctly patients with CM and was associated with elevated biomarkers of endothelial dysfunction and BBB disruption.