Increased PK11195 PET binding in the cortex of patients with MS correlates with disability
Increased PK11195 PET binding in the cortex of patients with MS correlates with disability
复制标题
DOI：
10.1212/wnl.0b013e3182635645
复制
发表时间：
2012-08-01
期刊：
影响因子：
9.9
通讯作者：
Piccini, Paola
中科院分区：
文献类型：
--
作者：
Politis, Marios;Giannetti, Paolo;Piccini, Paola
目的：激活的小胶质细胞被认为在多发性硬化(MS)皮质灰质(GM)脱髓鞘中起主要作用。我们的目的是评估MS患者体内皮质GM区小胶质细胞的激活情况，并探讨其与残疾程度的关系。方法：采用PET和优化的建模和分割程序，研究复发-缓解型MS(RRMS)患者、继发性进展型MS(SPMS)患者和健康对照组的皮质C-11-PK11195(PK11195)结合情况。用扩展残疾状态量表(EDSS)和多发性硬化症影响量表(MSIS-29)评定残疾程度。结果：与对照组相比，MS患者皮质GM PK11195结合增加，多灶性，在中央后回、额中回、眶前回、梭形回和海马旁回最高。SPMS患者的中央前回、顶上回、舌回、前上回、内侧回和下回也有增加。皮质GM PK11195总结合量与EDSS评分相关，与SPMS患者亚组的相关性更强。在SPMS患者中，PK11195结合也与MSIS-29评分相关。未发现PK11195在白质中的结合与残疾程度相关。EDSS评分越高，RRMS患者中央后回GMPK11195结合水平越高，SPMS患者中央前回GMPK11195结合水平越高。结论：MS患者皮质GM中小胶质细胞的激活可以在体内进行评估。这种分布并不均匀，而且与临床残疾有关。我们推测，PK11195结合的增加对应于死后SPMS皮质GM所描述的小胶质细胞激活的增强。神经病学(R)2012；79：523-530
Objective: Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.Methods: Using PET and optimized modeling and segmentation procedures, we investigated cortical C-11-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).Results: Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS.Conclusions: Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM. Neurology (R) 2012;79:523-530