Neuroinflammatory component of gray matter pathology in multiple sclerosis

作者：Herranz Elena; Gianni Costanza; Louapre Celine; Treaba Constantina A; Govindarajan Sindhuja T; Ouellette Russell; Loggia Marco L; Sloane Jacob A; Madigan Nancy; Izquierdo Garcia David; Ward Noreen; Mangeat Gabriel; Granberg Tobias; Klawiter Eric C; Catana Ciprian; Hooker Jacob M; Taylor Norman; Ionete Carolina; Kinkel Revere P; Mainero Caterina^*

来源：Annals of Neurology, 2016, 80(5): 776-790.

DOI：10.1002/ana.24791

ObjectiveIn multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with C-11-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.
MethodsFifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent C-11-PBR28 MR-PET. MS subjects underwent 7T <mml:msubsup>T2*</mml:msubsup>-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. C-11-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios.
ResultsRelative to controls, MS subjects exhibited abnormally high C-11-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, C-11-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased C-11-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels.
InterpretationIn MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790

• 出版日期2016-11