The neuroinflammatory component of gray matter pathology in multiple sclerosis

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 relapsing-remitting MS (RRMS) cases, and 14 matched healthy controls underwent (11) C-PBR28 MR-PET. MS subjects underwent 7 Tesla T2 *-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. This article is protected by copyright. All rights reserved.