Neuroinflammatory component of gray matter pathology in multiple sclerosis

Elena Herranz, Costanza Giannì, Céline Louapre, Constantina A. Treaba, Sindhuja T. Govindarajan, Russell Ouellette, Marco L. Loggia, Jacob A. Sloane, Nancy Madigan, David Izquierdo-Garcia, Noreen Ward, Gabriel Mangeat (+8 others)
2016 Annals of Neurology  
Objective-In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-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. Methods-Fifteen secondary-progressive MS (SPMS) and 12
more » ... relapsing-remitting MS (RRMS) cases, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7 Tesla T 2 *-weighted imaging for cortical lesions segmentation; neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60-90-minutes standardized uptake values and volume of distribution ratios. Results-Relative to controls, MS subjects exhibited abnormally high 11 C-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, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. Interpretation-In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, and closely linked to poor clinical outcome and, at least partly, to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Herranz et al.
doi:10.1002/ana.24791 pmid:27686563 pmcid:PMC5115951 fatcat:ypqdp4djyvg4lohly2ze5j5uz4