Author Of 2 Presentations
P0625 - Quantitative Susceptibility Mapping in the cortical ribbon of MS patients and its dependence on cortical thinning. (ID 1142)
Abstract
Background
Neuropathological examinations of multiple sclerosis (MS) brains indicate sub-pial cortical grey matter (GM) demyelination and damage occurring according to a “surface-in” gradient related to elevated levels of inflammation compartmentalized in sub-arachnoid spaces and meninges. Quantitative susceptibility mapping (QSM) is an MRI technique sensitive to changes in iron or myelin.
Objectives
To test the ability of QSM to detect and localize alterations in cortical iron/myelin content in MS and to investigate possible QSM alterations possibly caused by cortical thinning.
Methods
A group of 105 RR-MS patients (40.7±10.2 y mean±std; m:f 13:92; EDSS median 2 (0 - 6)) and 21 matched healthy controls (HC; 39.5±10.5 y; m:f 8:13) were examined by using 3T MRI 3D-EPI (0.5x0.5x0.5mm), 3D T1w (1x1x1mm) and a 3D FLAIR sequence (1x1x1mm). QSM was computed using a total generalized variation algorithm. T1 lesion filled images were analyzed with Freesurfer to reconstruct WM/GM and pial surfaces. QSM was sampled across the entire cortex with steps of 25% of cortical volume (0%: WM/GM, 100%: pial surface) and projected to the 32k vertices Conte-69 template. Group-wise QSM differences were performed by a permutation-based ANOVA test employing threshold-free cluster enhancement to correct for multiple comparisons (p<0.05 FWE corrected). A vertex-wise cortical thickness (CTh) regressor was used to investigate the impact of cortical thinning on QSM alterations.
Results
Significant differences in QSM showing higher susceptibility in RR-MS than HC were present in majority in cerebral sulci (21, 55 and 55% at 25, 50 and 75%) compared to gyri (9, 37, 38% at 25, 50 and 75%) and in the outer portion of the cortex compared to the inner cortex. The percentage of vertices significantly altered was higher in the outer layer (75%) respect to the inner ones (25%) in several regions, including portions of temporal and parietal lobes, precuneus and para- and post-central sulcus. The use of the CTh regressor, showed significant alterations in the same regions, and revealed further alterations of the cingulate cortex.
Conclusions
Surface analysis of QSM exhibits the presence of increase susceptibility in the cortex of MS patients compared to HC: the alterations are more extended in the outer layers of the cortical ribbon than the inner ones, supporting the hypothesis of a “surface-in” gradient of iron/myelin alterations in the cortex of MS patients. Moreover, these differences were not entirely explained by the presence of cortical thinning.
P0950 - Cerebrospinal fluid IgM associates with specific inflammatory profile and disease features in early multiple sclerosis. (ID 1739)
Abstract
Background
Patients with multiple sclerosis (MS) displayed high levels of IgM, IgA and IgG in the cerebrospinal fluid (CSF). In particular, intrathecal immunoglobulin M (IgM) synthesis has been suggested as a prognostic marker of a more rapid and severe disease progression in MS.
Objectives
Investigate whether IgM production is associated with a specific CSF inflammatory profile in naïve MS patients at the time of diagnosis.
Methods
CSF protein levels of IgM, IgA, IgG and of 34 inflammatory mediators were analysed using Bio-Plex Multiplex immunoassay in 103 naïve relapsing-remitting MS patients (RRMS) and 36 patients with other neurological disorders.CSF IgM levels were also correlated with clinical and neuroradiological measures (advanced 3T-MRI parameters) at diagnosis and after 2 years of follow-up.
Results
A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p=0.013), while no significant differences in IgG (p=0.360) and IgA (p=0.700) levels between the two groups have been detected. CSF IgM levels correlated with higher paired CSF levels of CXCL13 (p=0.039), CCL21 (p=0.023), IL-10 (p=0.025), IL-12p70 (p=0.020), CX3CL1 (p=0.036) and CHI3L1 (p=0.048) and were associated with earlier age of patients at diagnosis (p=0.008), white matter lesions (WMLs) number (p=0.039) and disease activity (p=0.033) after 2 years of follow-up.
Conclusions
IgM are the most abundant immunoglobulins present at diagnosis in naïve RRMS patients compared to other neurological conditions at the time of diagnosis and their association with further molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1 and CHI3L1) suggestsa link between humoral and innate intrathecal immunity.