Centre for Neuroscience, Hammersmith Hospital, Imperial College London, London.
Neurology. 2012 Aug 7;79(6):523-30. doi: 10.1212/WNL.0b013e3182635645. Epub 2012 Jul 3.
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.
Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-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).
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.
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.
研究认为激活的小胶质细胞在多发性硬化症（MS）皮质灰质（GM）脱髓鞘中起主要作用。我们的目的是评估MS 患者皮质 GM 中的小胶质细胞激活，并探讨其与残疾评估的关系。
使用 PET 和优化的建模和分割程序，我们研究了复发缓解型 MS（RRMS）患者、继发进展型 MS（SPMS）患者和健康对照者的皮质（11）C-PK11195（PK11195）结合。残疾采用扩展残疾状态量表（EDSS）和多发性硬化症影响量表（MSIS-29）进行评估。
MS 患者的皮质 GM PK11195 结合相对于对照组增加，呈多灶性，最高见于中央后回、中额回、前眶回、梭状回和海马旁回。SPMS 患者的中央前回、上顶叶、舌回和前上回、内侧和下颞回也出现了额外的增加。皮质 GM PK11195 总结合与 EDSS 评分相关，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。在 SPMS 患者中，皮质 GM PK11195 结合与 EDSS 评分呈正相关，而在 RRMS 患者中，皮质 GM PK11195 结合与中央后回相关，在 SPMS 患者中，皮质 GM PK11195 结合与中央前回相关。
MS 患者皮质 GM 中的小胶质细胞激活可在体内进行评估。分布不均匀，与临床残疾有关。我们推测，增加的 PK11195 结合对应于尸检 SPMS 皮质 GM 中描述的增强的小胶质细胞激活。
