The role of activated microglia in multiple sclerosis and clinically isolated syndromes: neuroimaging studies
File(s)
Author(s)
Giannetti, Paolo
Type
Thesis
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.
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.
Version
Open Access
Date Issued
2015-05
Date Awarded
2016-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Nicholas, Richard
Piccini, Paola
Sponsor
European Federation of Neurological Societies
Federazione Italiana Sclerosi Multipla
Grant Number
FISM: Cod. 2010/B/7
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)