区域小胶质细胞在黑质中的激活与 MS 的疲劳有关。
Regional microglial activation in the substantia nigra is linked with fatigue in MS.
机构信息
From the Partners MS Center (T.S., S.C., K.C., B.G., R.B., H.L.W.), Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; PET Imaging Program in Neurologic Diseases (T.S., S.C., K.C.), Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Functional Neuroimaging Laboratory (H.P., R.B., D.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Division of Nuclear Medicine and Molecular Imaging (S.D., M.-A.P., M.K.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Laboratory for Neuroimaging Research (R.C., S.T.), Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Medicine (S.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Ceretype Neuromedicine (E.S.)Department of Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2020 Aug 7;7(5). doi: 10.1212/NXI.0000000000000854. Print 2020 Sep 3.
OBJECTIVE
The goal of our study is to assess the role of microglial activation in MS-associated fatigue (MSAF) using [F-18]PBR06-PET.
METHODS
Fatigue severity was measured using the Modified Fatigue Impact Scale (MFIS) in 12 subjects with MS (7 relapsing-remitting and 5 secondary progressive) and 10 healthy control participants who underwent [F-18]PBR06-PET. The MFIS provides a total fatigue score as well as physical, cognitive, and psychosocial fatigue subscale scores. Standardized Uptake Value (SUV) 60-90 minute frame PET maps were coregistered to 3T MRI. Voxel-by-voxel analysis using Statistical Parametric Mapping and atlas-based regional analyses were performed. SUV ratios (SUVRs) were global brain normalized.
RESULTS
Peak voxel-based level of significance for correlation between total fatigue score and PET uptake was localized to the right substantia nigra (T-score 4.67, = 0.001). Similarly, SUVRs derived from atlas-based segmentation of the substantia nigra showed significant correlation with MFIS (r = 0.76, = 0.004). On multiple regression, the right substantia nigra was an independent predictor of total MFIS ( = 0.02) and cognitive MFIS subscale values ( = 0.007), after adjustment for age, disability, and depression. Several additional areas of significant correlations with fatigue scores were identified, including the right parahippocampal gyrus, right precuneus, and juxtacortical white matter (all < 0.05). There was no correlation between fatigue scores and brain atrophy and lesion load in patients with MS.
CONCLUSION
Substantia nigra microglial activation is linked to fatigue in MS. Microglial activation across key brain regions may represent a unifying mechanism for MSAF, and further evaluation of neuroimmunologic basis of MSAF is warranted.
目的
本研究旨在通过 [F-18]PBR06-PET 评估小胶质细胞激活在多发性硬化症相关疲劳（MSAF）中的作用。
方法
12 名多发性硬化症患者（7 名复发缓解型，5 名继发进展型）和 10 名健康对照者接受了 [F-18]PBR06-PET，使用改良疲劳影响量表（MFIS）评估疲劳严重程度。MFIS 提供总疲劳评分以及身体、认知和心理社会疲劳子量表评分。60-90 分钟 PET 扫描的标准化摄取值（SUV）与 3T MRI 配准。使用统计参数映射和基于图谱的区域分析进行体素-体素分析。对 SUV 比值（SUVR）进行全脑标准化。
结果
总疲劳评分与 PET 摄取之间相关性的体素水平的峰值显著定位于右侧黑质（T 分数 4.67， = 0.001）。同样，基于黑质图谱分割的 SUVR 与 MFIS 显著相关（r = 0.76， = 0.004）。多元回归分析显示，调整年龄、残疾和抑郁因素后，右侧黑质是总 MFIS（ = 0.02）和认知 MFIS 子量表值（ = 0.007）的独立预测因子。还确定了与疲劳评分显著相关的其他几个区域，包括右侧海马旁回、右侧楔前叶和皮质下白质（均 < 0.05）。多发性硬化症患者的疲劳评分与脑萎缩和病变负荷无相关性。
结论
黑质小胶质细胞激活与多发性硬化症的疲劳有关。关键脑区的小胶质细胞激活可能代表 MSAF 的统一机制，进一步评估 MSAF 的神经免疫基础是必要的。
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