The role of activated microglia in multiple sclerosis and clinically isolated syndromes: neuroimaging studies

Abstract

Background. Multiple sclerosis (MS) has been traditionally described as an autoimmune disease of adaptive immunity affecting the white matter (WM) of central nervous system. Recent scientific interest has focused on the role of the innate immunity and structures including the normal-appearing WM (NAWM), grey matter (GM) and black holes (BH). PET imaging using [11C]-PK11195 (PK), allows the in vivo visualization of activated microglia. Aims. This project aims to study in vivo the role of microglia activation in three specific structures, BH, GM and NAWM and, in a wide range of patients, from clinically isolated syndromes (CIS) to the later stages of progressive course. This study also aims to identify prognostic factors which could be useful as indicators for early treatment and in later stages for disability progression. Methods. Subjects: twenty MS, 18 CIS and 8 healthy controls (HC). Procedures: clinical history, neurological examination, PK-PET and MRI scans. MS subjects have been followed up only clinically, while CIS also with repeated MRI, yearly, for 2 years. The PK binding potential is referred to the non-displaceable radioligand (PKBPND). Results. In progressive patients BH PKBPND correlated with disability and represented a significant predictor of disability. In NAWM the PKBPND was increased in patients compared with HC and within the MS subgroups it increased with the stage. In CIS subjects PKBPND was predictive of MS diagnosis at 2 years and in progressive patients of worse clinical outcome. GM central structures (CS) showed increased PKBPND in CIS vs HC. A prognostic value for the cortex is reported in progressive patients. Discussion: PK-PET imaging has shown new insights into BH, NAWM and GM structures that are relevant for the understanding of MS pathology. This includes the relevance of activated microglia in BH, in CIS NAWM and CS, in MS cortical GM as a predictor for clinical progression.