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通过[F]-DPA714正电子发射断层显像(PET)可视化的小胶质细胞激活是抗LGI1脑炎严重程度和预后的潜在标志物。

Microglial Activation Visualized by [F]-DPA714 PET Is a Potential Marker of Severity and Prognosis for Anti-LGI1 Encephalitis.

作者信息

Wang Jingguo, Ge Jingjie, Deng Bo, Lin Huamei, Yang Wenbo, Sheng Tianyang, Tang Weijun, Yu Hai, Zhang Xiang, Li Yarong, Liu Xiaoni, Zuo Chuantao, Chen Xiangjun

机构信息

Department of Neurology and Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

National Center for Neurological Disorders, Shanghai, China.

出版信息

Eur J Neurol. 2025 Mar;32(3):e70107. doi: 10.1111/ene.70107.

Abstract

BACKGROUND AND PURPOSE

Whether microglial activation plays an important role in the pathogenesis of autoimmune encephalitis (AE), such as anti-leucine-rich, glioma-inactivated-1 (LGI1) encephalitis, remains unknown. [F]-DPA714 PET targeting the translocator protein (TSPO) is a novel method to detect neuroinflammation via visualizing activated microglia. In this study, we aimed to investigate the application of [F]-DPA714 PET in anti-LGI1 encephalitis.

METHODS

Patients with anti-LGI1 encephalitis and non-inflammatory controls (NIC) underwent [F]-DPA714 PET scans were enrolled. Standardized uptake value ratios normalized to the cerebellum (SUVRc) in LGI1-AE patients were calculated for semi-quantitative analysis. The microglial activation marker, soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was measured in cerebrospinal fluid (CSF) to demonstrate its correlation with [F]-DPA714 PET imaging. Logistic regression analysis was used to identify potential predictors of prognosis.

RESULTS

Forty-six patients with anti-LGI1 encephalitis were included in this study. Increased TSPO uptake was identified in the hippocampus, frontal cortex, and caudate nucleus. Montreal Cognitive Assessment (MoCA) score was significantly correlated with SUVRc in the hippocampus (R = 0.13, p = 0.034) and frontal cortex (R = 0.13, p = 0.017). Overexpressed sTREM2 in CSF was correlated with SUVRc in the hippocampus (R = 0.18, p = 0.04). SUVRc in the hippocampus significantly decreased after immunotherapy and was associated with improvement of MoCA score (R = 0.54, p = 0.023). Increased SUVRc in the frontal cortex and hippocampus was associated with unfavorable disability recovery (odds ratio [OR] = 7.1, 95% CI 1.67-29.9, p = 0.008) and persistent amnesia (OR = 5.4, 95% CI 1.3-22.2, p = 0.021) respectively.

CONCLUSION

Microglial activation visualized by [F]-DPA714 PET is associated with clinical features and may be used as a potential biomarker for therapeutic and prognostic evaluation.

摘要

背景与目的

小胶质细胞激活在自身免疫性脑炎(AE),如抗富含亮氨酸胶质瘤失活1蛋白(LGI1)脑炎的发病机制中是否起重要作用仍不清楚。靶向转运蛋白(TSPO)的[F]-DPA714 PET是一种通过可视化激活的小胶质细胞来检测神经炎症的新方法。在本研究中,我们旨在探讨[F]-DPA714 PET在抗LGI1脑炎中的应用。

方法

纳入接受[F]-DPA714 PET扫描的抗LGI1脑炎患者和非炎症对照(NIC)。计算LGI1-AE患者以小脑为标准的标准化摄取值比率(SUVRc)进行半定量分析。检测脑脊液(CSF)中髓样细胞表达的可溶性触发受体2(sTREM2)这一小胶质细胞激活标志物,以证明其与[F]-DPA714 PET成像的相关性。采用逻辑回归分析确定预后的潜在预测因素。

结果

本研究纳入了46例抗LGI1脑炎患者。在海马体、额叶皮质和尾状核中发现TSPO摄取增加。蒙特利尔认知评估(MoCA)评分与海马体(R = 0.13,p = 0.034)和额叶皮质(R = 0.13,p = 0.017)的SUVRc显著相关。CSF中sTREM2过表达与海马体的SUVRc相关(R = 0.18,p = 0.04)。免疫治疗后海马体的SUVRc显著降低,并与MoCA评分的改善相关(R = 0.54,p = 0.023)。额叶皮质和海马体中SUVRc升高分别与不良的残疾恢复(优势比[OR]=7.1,95%可信区间1.67 - 29.9,p = 0.008)和持续性失忆(OR = 5.4,95%可信区间1.3 - 22.2,p = 0.021)相关。

结论

[F]-DPA714 PET可视化的小胶质细胞激活与临床特征相关,可作为治疗和预后评估的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3208/11886409/7a0e03ede904/ENE-32-e70107-g005.jpg

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