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正电子发射断层扫描研究:肌萎缩侧索硬化症运动皮层中氧化应激增加与疾病严重程度相关

Increased oxidative stress is related to disease severity in the ALS motor cortex: A PET study.

作者信息

Ikawa Masamichi, Okazawa Hidehiko, Tsujikawa Tetsuya, Matsunaga Akiko, Yamamura Osamu, Mori Tetsuya, Hamano Tadanori, Kiyono Yasushi, Nakamoto Yasunari, Yoneda Makoto

机构信息

From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.

出版信息

Neurology. 2015 May 19;84(20):2033-9. doi: 10.1212/WNL.0000000000001588. Epub 2015 Apr 22.

DOI:10.1212/WNL.0000000000001588
PMID:25904686
Abstract

OBJECTIVE

To investigate cerebral oxidative stress based on an over-reductive state caused by mitochondrial dysfunction and its relationship to disease severity in patients with amyotrophic lateral sclerosis (ALS) using PET with [(62)Cu]diacetyl-bis(N(4)-methylthiosemicarbazone) ((62)Cu-ATSM).

METHODS

Twelve patients with ALS and 9 age-matched healthy controls underwent a 20-minute dynamic brain PET scan after (62)Cu-ATSM injection. The standardized uptake value (SUV) images obtained from the last 10 minutes of frames were normalized by the global mean (nSUV). Regional (62)Cu-ATSM retention in the nSUV images was compared between groups using statistical parametric mapping (SPM) and region of interest (ROI) analysis. Secondary analyses evaluated the correlations between regional nSUVs and the clinical characteristics of the participants.

RESULTS

In SPM mapping, patients with ALS showed a significantly greater accumulation of (62)Cu-ATSM compared to controls in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. ROI analysis also revealed significantly greater nSUVs in patients than controls in these regions. Increases in nSUV for these regions were associated with decreases in the revised ALS Functional Rating Scale score, suggesting a good correlation with the severity of ALS. In controls, age was correlated with nSUV for the bilateral cortices around the central sulcus, although this correlation was not observed in patients with ALS.

CONCLUSIONS

(62)Cu-ATSM PET imaging demonstrated increased oxidative stress based on an over-reductive state, primarily in the motor cortex, in patients with ALS. The magnitude of oxidative stress correlated well with clinical severity, indicating that it may be associated with neurodegenerative changes in ALS.

摘要

目的

使用[(62)Cu]双乙酰双(N(4)-甲基硫代半卡巴腙)((62)Cu-ATSM)正电子发射断层扫描(PET),研究肌萎缩侧索硬化症(ALS)患者基于线粒体功能障碍导致的过度还原状态的脑氧化应激及其与疾病严重程度的关系。

方法

12例ALS患者和9例年龄匹配的健康对照在注射(62)Cu-ATSM后接受了20分钟的动态脑PET扫描。从最后10分钟的图像帧中获得的标准化摄取值(SUV)图像通过全局均值进行归一化(nSUV)。使用统计参数映射(SPM)和感兴趣区域(ROI)分析比较了两组nSUV图像中区域(62)Cu-ATSM的滞留情况。二次分析评估了区域nSUV与参与者临床特征之间的相关性。

结果

在SPM映射中,与对照组相比,ALS患者在中央沟周围的双侧皮质,包括运动皮质和右侧顶上小叶,显示出(62)Cu-ATSM的显著积累。ROI分析也显示这些区域患者的nSUV明显高于对照组。这些区域nSUV的增加与修订的ALS功能评定量表评分的降低相关,表明与ALS的严重程度有良好的相关性。在对照组中,年龄与中央沟周围双侧皮质的nSUV相关,尽管在ALS患者中未观察到这种相关性。

结论

(…此处为重复内容,不再重复翻译)Cu-ATSM PET成像显示ALS患者基于过度还原状态的氧化应激增加,主要在运动皮质。氧化应激的程度与临床严重程度密切相关,表明它可能与ALS的神经退行性变化有关。

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