Li Qianwen, Zhu Wenjia, Wen Xinmei, Zang Zhenxiang, Da Yuwei, Lu Jie
Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China.
Front Neurol. 2022 Feb 24;13:791300. doi: 10.3389/fneur.2022.791300. eCollection 2022.
Previous studies have reliably identified iron deposition in the motor cortex as potential pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we intended to investigate iron deposition, gray matter (GM) atrophy, and their associations with disease severity in the motor cortex and the thalamus in patients with ALS.
A total of 34 patients with ALS (age 51.31 ± 8.24 years, 23 males) and 34 nonneurological controls (age 50.96 ± 9.35 years, 19 males) were enrolled between 2018 and 2020. The Revised ALS Functional Rating Scale (ALSFRS-R) and the Penn upper motor neuron (UMN) score were measured. MRI data included quantitative susceptibility mapping (QSM) for iron deposition and three-dimensional (3D) T1 for gray matter volume. After a between-group comparison, Pearson's correlation coefficient was used for identifying correlations of iron deposition, GM volume, and clinical measurements.
The two-sample -tests revealed increased iron deposition in the left precentral gyrus (peak voxel = 4.78, = 0.03) and the thalamus (peak voxel: right: = 6.38, < 0.001; left: = 4.64, = 0.02) in patients with ALS. GM volume of the precentral gyrus ( = -2.42, = 0.02) and the bilateral thalamus ( = -4.10, < 0.001) were reduced. Negative correlations were found between the increased QSM values and the decreased GM volume ( < 0.04, one-tailed) in patients with ALS. Iron deposition in the left precentral gyrus was positively correlated with the UMN score ( = 0.40, = 0.02) and the GM volume was negatively correlated with the UMN score ( = -0.48, = 0.004). Negative correlation between thalamic iron deposition and the ALSFRS-R ( = -0.36, = 0.04) score was observed.
Iron deposition in the thalamus, in addition to the motor cortex, is accompanied by GM atrophy and is associated with disease severity in patients with ALS, indicating that the thalamus is also a pathological region in patients with ALS.
以往研究已可靠地确定运动皮质中的铁沉积是肌萎缩侧索硬化症（ALS）的潜在发病机制。在此，我们旨在研究ALS患者运动皮质和丘脑中的铁沉积、灰质（GM）萎缩及其与疾病严重程度的关联。
2018年至2020年期间共纳入34例ALS患者（年龄51.31±8.24岁，男性23例）和34名非神经学对照者（年龄50.96±9.35岁，男性19例）。测量修订的ALS功能评定量表（ALSFRS-R）和宾夕法尼亚上运动神经元（UMN）评分。MRI数据包括用于铁沉积的定量磁化率成像（QSM）和用于灰质体积的三维（3D）T1加权成像。在进行组间比较后，使用Pearson相关系数来确定铁沉积、GM体积和临床测量值之间的相关性。
双样本t检验显示，ALS患者左侧中央前回（峰值体素=4.78，P=0.03）和丘脑中的铁沉积增加（峰值体素：右侧：P=6.38，P<0.001；左侧：P=4.64，P=0.02）。中央前回（P=-2.42，P=0.02）和双侧丘脑（P=-4.10，P<0.001）的GM体积减小。在ALS患者中，QSM值增加与GM体积减小之间存在负相关（P<0.04，单尾）。左侧中央前回的铁沉积与UMN评分呈正相关（P=0.40，P=0.02），GM体积与UMN评分呈负相关（P=-0.48，P=0.004）。观察到丘脑铁沉积与ALSFRS-R评分之间存在负相关（P=-0.36，P=0.04）。
除运动皮质外，丘脑中的铁沉积还伴有GM萎缩，并与ALS患者的疾病严重程度相关，表明丘脑也是ALS患者的一个病理区域。
