Journal of Neurology, Neurosurgery & Psychiatry:神经炎症预示进行性核上麻痹的疾病进展

2021-06-23 MedSci原创 MedSci原创

小胶质细胞激活的PET分子成像和tau病理可以预测PSP的临床进展。这些数据鼓励了对免疫调节方法的评估，以治疗疾病的PSP和潜在的PET分层患者在早期临床试验。

进行性核上麻痹(PSP)除了tau病理和神经元丧失外，还会发生神经炎症。然而，体内成像标记物对PSP中这些过程的预后价值仍不清楚。

Journal of Neurology, Neurosurgery & Psychiatry杂志最近发表研究论文，检验了皮质下神经炎症的基线体内成像评估可以预测PSP患者的临床进展这一主要假设。

该研究的主要假设是，与PSP病理相关的皮质下区域的炎症促进了疾病的进展。测试了神经炎症的体内基线测量([¹¹C]PK11195 PET)是否可以预测PSP-Richardson综合征患者的年临床进展率。测试了关于基线皮质炎症、tau病理([¹⁸F]AV-1451 PET)和区域脑容量(结构MRI)的预测价值的次级假设。

灰质体积，炎症和tau病理的主成分（PCs）。灰质体积的前四个PCs(左图)，[¹¹C]PK11195 BPND(中间图)和[¹⁸F]AV-1451 BPND(右图)。颜色代表每个组件的大脑区域的roated重量(范围:从−1到1)。

17例PSP-Richardson综合征患者接受了基线多模态成像评估，包括[¹¹C]PK11195正电子发射断层扫描(PET)以指示小胶质细胞活化，[¹⁸F]AV-1451 PET用于tau病理和结构MRI。用进行性核上麻痹评分量表(PSPRS)(平均间隔5个月)在基线和连续4年测量疾病的严重程度。

用三主成分分析(PCA)总结了区域灰质体积和PET配体结合潜力。纵向PSPRS评分采用线性混合效应模型。单模态成像预测因子与个体估计的进展率进行回归，以确定基线成像标记物的预后价值。

PSPRS随时间变化的临床严重程度。彩色线表示个体患者PSPRS评分的时间进程。黑线表示组级的线性拟合。

炎症和tau PET标记物与临床严重程度和进展相关。PSPRS分数(上行)和截距PSPRS分数(下行)对每种特异性主成分(经协变量修正的X轴残差分量值)的基线分数的年度变化的显著回归分析:[¹¹C]PK11195 PET(左面板)和[¹⁸F]AV-1451 PET(右面板)。以年龄、教育程度和性别为协变量，报告了每种模型的估计参数。

反映脑干和小脑神经炎症和tau蛋白负担的PCA成分与PSPRS随后的年变化率相关。神经炎症和tau病理的PCA衍生PET标记物与同一区域的区域脑容量相关。然而，仅MRI体积并不能预测临床进展的速率。

该研究的主要发现是，皮质下神经炎症与基线PSP的临床严重程度，并与更快的后续临床进展相关。在皮层下tau病理评估中也发现了类似的效应，与PSP中[¹⁸F]AV1451结合的解释相关。PET标记物彼此相关，并与同一区域萎缩的结构性MRI测量相关联。然而，皮层下灰质体积与随后的临床进展不相关，也与基线时的临床严重程度不显著相关。同样，基线时的临床严重程度并不能预测接下来几年的临床进展，这表明在疾病的不同阶段，临床变化的年速率大约是恒定的。

总之，该研究结果支持神经炎症与PSP-Richardson综合征进展的相关性。[¹¹C]PK11195可能是PSP临床试验的一个有价值的生物标志物，可以作为结构性MRI的补充。PET标记物可用于基于预后的患者分层和治疗反应的评估，支持PSP疾病改善治疗的免疫调节策略（，单独或联合针对tau蛋白和其他致病途径的治疗）的发展。

原文出处

Malpetti M, Passamonti L, Jones PS, et al.Neuroinflammation predicts disease progression in progressive supranuclear palsy. Journal of Neurology, Neurosurgery & Psychiatry 2021;92:769-775. https://jnnp.bmj.com/content/92/7/769

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2022-03-29 liye789132262

#神经炎#

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2022-03-22 ligang4439

#进行性#

41 0
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2022-06-02 diushouji

#Psychiatry#

47 0
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2022-03-27 12498c32m68暂无昵称

#GER#

38 0
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2021-07-26 yinhl1978

#Neurol#

38 0
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2021-08-15 chg121

#surgery#

48 0
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2021-09-08 mjldent

#疾病进展#

34 0
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2021-06-25 lsndxfj

#ROS#

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Journal of Neurology, Neurosurgery & Psychiatry:神经炎症预示进行性核上麻痹的疾病进展

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