Pei Xun, Bai Xiaoyan, Zhang Xue, Hu Zhangxuan, Wang Wei, Zhang Xueyan, Zhang Yingkui, Tang Hefei, Zhang Yaqing, Yu Xueying, Yuan Ziyu, Zhang Peng, Chen Tong, Zhao Yuanbin, Jia Xiuqin, Yang Qi, Wang Yonggang, Sui Binbin
Tiantan Neuroimaging Center for Excellence, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
BMC Med. 2025 May 28;23(1):300. doi: 10.1186/s12916-025-04125-8.
Abnormal iron deposition may be a biomarker for a disrupted central antinociceptive neuronal network, and the relationship between iron deposition and the pathophysiological mechanisms of chronic migraine (CM) with medication overuse (MOH) remains unclear. We investigated iron deposition in the deep gray matter (DGM) of the brain in CM patients with and without MOH using quantitative susceptibility mapping (QSM).
Forty-eight healthy controls (HCs) and 69 CM patients (36 with MOH; 33 without MOH) were recruited. QSM data were acquired using a 3.0 T Magnetic resonance imaging (MRI). Regions of interest (ROI) in the DGM, including the bilateral caudate, putamen, globus pallidus (GP), hippocampus, nucleus accumbens, and amygdala, were segmented from the T1-weighted images (T1WI) of the whole brain of each individual patient using FreeSurfer. QSM images were registered to T1WI. QSM values within each ROI were extracted and compared between CM and HCs, as well as between CM with MOH and CM without MOH. Correlations between QSM values and clinical assessment scale scores were calculated. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of QSM values in these DGM for detecting CM and CM with MOH.
Compared to HCs, CM patients exhibited increased iron deposition in the caudate (p = 0.013) and putamen (p < 0.001). In the CM without MOH group, headache duration correlated positively with iron deposition in the caudate (r = 0.502, p = 0.010) and putamen (r = 0.514, p = 0.009). CM with MOH patients showed greater iron deposition in the caudate (p < 0.001), putamen (p < 0.001), and GP (p = 0.049) than those without MOH, with medication use frequency correlating positively with iron deposition in the caudate (r = 0.427, p = 0.023) and putamen (r = 0.445, p = 0.018). ROC curve analysis indicated that the caudate (AUC = 0.736) and putamen (AUC = 0.729) exhibited high sensitivity and specificity in diagnosing CM with MOH.
CM patients with MOH had excessive iron deposition in basal ganglia regions, including the caudate, putamen, and GP, which may be related to the medication overuse behavior. Iron deposition in the caudate and putamen may be a potential biomarker for CM with MOH. These findings provide insight into the common pathophysiological mechanisms underlying MOH and potential addiction.
异常铁沉积可能是中枢抗伤害感受神经元网络紊乱的生物标志物，而铁沉积与慢性偏头痛（CM）伴药物过度使用（MOH）的病理生理机制之间的关系仍不清楚。我们使用定量磁化率成像（QSM）研究了有和没有MOH的CM患者脑深部灰质（DGM）中的铁沉积情况。
招募了48名健康对照者（HCs）和69名CM患者（36名伴有MOH；33名不伴有MOH）。使用3.0T磁共振成像（MRI）获取QSM数据。使用FreeSurfer从每位患者全脑的T1加权图像（T1WI）中分割出DGM中的感兴趣区域（ROI），包括双侧尾状核、壳核、苍白球（GP）、海马体、伏隔核和杏仁核。将QSM图像配准到T1WI。提取每个ROI内的QSM值，并在CM和HCs之间以及伴有MOH的CM和不伴有MOH的CM之间进行比较。计算QSM值与临床评估量表评分之间的相关性。使用受试者工作特征（ROC）分析评估这些DGM中QSM值对检测CM和伴有MOH的CM的诊断性能。
与HCs相比，CM患者尾状核（p = 0.013）和壳核（p < 0.001）中的铁沉积增加。在不伴有MOH的CM组中，头痛持续时间与尾状核（r = 0.502，p = 0.010）和壳核（r = 0.514，p = 0.009）中的铁沉积呈正相关。伴有MOH的CM患者在尾状核（p < 0.001）、壳核（p < 0.001）和GP（p = 0.049）中的铁沉积比不伴有MOH的患者更多，药物使用频率与尾状核（r = 0.427，p = 0.023）和壳核（r = 0.445，p = 0.018）中的铁沉积呈正相关。ROC曲线分析表明，尾状核（AUC = 0.736）和壳核（AUC = 0.729）在诊断伴有MOH的CM时具有较高的敏感性和特异性。
伴有MOH的CM患者在基底神经节区域，包括尾状核、壳核和GP中存在过量铁沉积，这可能与药物过度使用行为有关。尾状核和壳核中的铁沉积可能是伴有MOH的CM的潜在生物标志物。这些发现为MOH和潜在成瘾的共同病理生理机制提供了见解。
