脑桥周边灰质铁沉积作为慢性偏头痛潜在生物标志物。

Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine.

机构信息

From the Departments of Neurology (C.D., A.L., X.R.-O., R.L.) and Radiology (C.V.), Hospital Clinico Universitario, Universidade de Santiago de Compostela; Clinical Neurosciences Research Laboratory (A.V.-P., M.P.-M., T.S., F.C., J.C., R.L.), Health Research Institute of Santiago de Compostela; Magnetic Resonance Imaging (P.R.-C.), Molecular Imaging Unit, CIC biomaGUNE, Donostia-San Sebastian; and Ikerbasque (P.R.-C.), The Basque Foundation for Science, Bilbao, Spain.

出版信息

Neurology. 2019 Mar 5;92(10):e1076-e1085. doi: 10.1212/WNL.0000000000007047. Epub 2019 Feb 1.

DOI:10.1212/WNL.0000000000007047

PMID:30709968

Abstract

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 μL, < 0.001) and controls (70.2 ± 6.8 vs 15.1 ± 10.8 μL, < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 ± 6.5 vs 249.7 ± 6.9 μL, < 0.001) and controls (360.3 ± 6.5 vs 168.6 ± 10.3 μL, < 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 μL in RN (80% sensitivity, 71% specificity) and 240 μL in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor-like WEAK ( = 0.395, = 0.005) and cellular fibronectin ( = 0.294, = 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.

摘要

目的

研究红核（RN）、苍白球（GP）和导水管周围灰质（PAG）中铁沉积作为慢性偏头痛（CM）的潜在生物标志物及其与偏头痛病理生理学相关生物标志物水平的关系。

方法

本病例对照研究纳入了 112 名偏头痛患者（55 名 CM，57 名发作性偏头痛 [EM]）和 25 名无头痛对照者。我们使用 3T MRI 和 NIH 软件平台 ImageJ 分析铁沉积；在发作间期，通过 ELISA 分析外周血中炎症、内皮功能障碍和血脑屏障（BBB）破坏的标志物水平。

结果

与 EM 患者（70.2±6.8 vs. 25.5±7.3 μL，<0.001）和对照组（70.2±6.8 vs. 15.1±10.8 μL，<0.001）相比，CM 患者的 RN 铁沉积体积更大，与 EM 患者（360.3±6.5 vs. 249.7±6.9 μL，<0.001）和对照组（360.3±6.5 vs. 168.6±10.3 μL，<0.001）相比，PAG 中的铁沉积也更多。EM 患者与对照组之间在 PAG 中也存在显著差异。GP 无显著差异。受试者工作特征曲线显示，RN 中铁沉积体积的最佳阈值为 15 μL（80%敏感性，71%特异性），PAG 为 240 μL（93%敏感性，97%特异性）。PAG 中的铁沉积体积与较高的血浆可溶性肿瘤坏死因子样弱相关物（ = 0.395， = 0.005）和细胞纤维连接蛋白（ = 0.294， = 0.040）水平相关。