Author Of 2 Presentations
P0093 - Increased serum GFAP associates with microstructural white matter damage in multiple sclerosis (ID 1066)
Abstract
Background
Astrocytes and microglial cells are now recognized as active players in contributing to the diffuse neuroaxonal damage associated with disease progression of multiple sclerosis (MS). The serum level of glial fibrillary acidic protein (GFAP), a biomarker for astrocytic activation, is increased in MS and associated with the disease progression and disability. Similarly, diffusion tensor imaging (DTI) parameters for microstructural changes in brain, including demyelination and axonal loss, associate with disability. The association between brain DTI parameters and serum GFAP has not been previously explored in MS.
Objectives
To get insights into DTI-measurable pathological correlates of elevated serum GFAP in the normal appearing white matter (NAWM) of MS.
Methods
A total of 62 MS patients with mean age of 49.4 years were included in the study. Study patients underwent DTI-MRI and blood sampling for GFAP determination by single molecule array (Simoa). MS patients were subdivided to GFAP(high) and GFAP(low) groups based on the median value of GFAP (97.7 pg/ml). Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the NAWM and six segmented NAWM regions. The associations between the DTI parameters and GFAP levels were analyzed within the GFAP(high) and GFAP(low) subgroups using Spearman correlation analysis and multiple regression model with sex and disease modifying treatment (no, 1st line or 2nd line) as adjustments performed with the R statistical software (version 4.0.0).
Results
Elevated serum GFAP levels correlated significantly with decreased FA values within the entire, frontal, temporal and cingulate NAWM (R=-0.39, p=0.03; R=-0.42, p=0.02; R=-0.37; p=0.04 and R=-0.38, p=0.03) and increased MD and RD within the frontal NAWM (R=0.36, p=0.046 for both) in the GFAP(high) subgroup. Associations between higher GFAP and lower FA in frontal and cingulate NAWM were sustained in the multiple regression model corrected for confounding variables (standardized regression coefficient r = -0.29, p = 0.045 and r = -0.33, p = 0.025).
Conclusions
Our results give evidence that increased serum GFAP levels are associated with DTI-measurable micro-damage in the NAWM in MS. Our work supports the use of serum GFAP as a biomarker for MS pathology-related astrocytopathy and related diffuse white matter damage.
P0653 - The value of grey matter microglial activation measurement by TSPO-PET in predicting clinical disease progression in multiple sclerosis (ID 1431)
Abstract
Background
Conventional MRI has limitations when it comes to characterizing the grey matter pathology of MS. PET (positron emission tomography) imaging, on the other hand, can provide more precise information at the cellular level. [11C]PK11195 is a first generation translocator protein (TSPO) radioligand that has been used to study innate immune cell activation status in multiple sclerosis brain in vivo.
Objectives
Our aim was to analyse the MRI volumes and [11C]PK11195 signal of MS brain grey matter regions and to investigate how these variables connect with disability progression.
Methods
MRI (3 or 1.5 tesla) and [11C]PK11195 PET data from 71 MS patients and 18 healthy controls were examined for regional grey matter BPF (brain parenchymal fraction) and [11C]PK11195 DVR (distribution volume ratio). The following regions of interest were chosen: cerebral cortex, thalamus, caudate, putamen and pallidum. EDSS (Expanded Disability Status Scale) was available at baseline and after 3.4 ± 1.1 (mean ± SD) years of follow-up. The imaging variables were compared between MS patients and healthy controls, and forward type stepwise logistic regression was used to assess the best variables predicting disease progression.
Results
MS patients had lower BPF in the cortex, thalamus and caudate (P < 0.05) compared to controls. MS patients had higher [11C]PK11195 DVR in the thalamus and pallidum (P = 0.01 and P = 0.0099 respectively) compared to controls. Patients with EDSS progression (EDSS increase ≥ 1.0 at follow-up; or ≥ 0.5, if EDSS at baseline was ≥ 6.0) had lower BPF in the thalamus and caudate (P = 0.045 and P = 0.034 respectively) and higher DVR in the thalamus (P = 0.014) compared to patients with no EDSS progression. In the forward type stepwise logistic regression model DVR in the thalamus was the only measured imaging variable that remained a significant predictor of disease progression.
Conclusions
There are regional differences in [11C]PK11195 binding and atrophy in grey matter areas of the MS brain. [11C]PK11195 signal in the thalamus seems to have potential in predicting future MS disease course.