2023 American Academy of Neurology Abstract Website

Martina Rubin¹, Elisabetta Pagani², Loredana Storelli², Alessandro Meani², Paolo Preziosa³, Monica Margoni¹, Maria Rocca³, Massimo Filippi⁴
¹Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, ²Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, ³Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, ⁴Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University

Objective:

To explore the cortical and thalamic microstructural abnormalities in MS patients according to a progressive distance from the CSF and their clinical relevance.

Background:

A CSF-in gradient in cortical and thalamic damage has been suggested in multiple sclerosis (MS), possibly due to CSF-mediated pathological processes. However, this pattern of damage has not been explored in vivo and concurrently both in the cortex and in the thalamus yet.

Design/Methods:

Brain 3T-MRI sequences were acquired from 52 MS patients (33 relapsing-remitting [RR], 19 progressive [P]) and 56 healthy controls (HC). From 3DT1-weighted sequences, cortical layers sampled at 25%-50%-75% depths from white matter (WM)-cortical interface (Freesurfer) and thalamic concentric bands at 1-2-3-voxels from ventricular-thalamus interface (in-house implemented method) were derived. Between-group comparisons of magnetization transfer ratio (MTR) values, as myelination index in cortical and thalamic layers and their correlations with clinical and structural measures were evaluated using linear mixed models and Spearman correlations.

Results:

Compared with HC, RRMS and PMS patients showed significantly lower MTR values in the most superficial cortical layer (RRMS=-1.23%, p=0.006, PMS=-1.70%, p=0.002), without between-group differences. Compared to HC, RRMS and PMS patients showed significantly lower MTR values in the band closest to the ventricles (RRMS=-1.63%, p=0.015, PMS=-3.62%, p<0.001). PMS showed also a significantly lower MTR in ventricle-closest band compared to RRMS (p=0.022) and in the second band compared to HC (-1.07%, p=0.048). Lower MTR values of CSF-closest cortical and thalamic layers were significantly correlated with longer disease duration, higher Expanded Disability Status Scale (EDSS) score, higher WM lesion volume (r from -0.45 to -0.35, p≤0.011), lower normalized brain, thalamic and cortical volumes (r from 0.42 to 0.56, p≤0.002).

Conclusions:

In MS, a clinically-relevant CSF-in gradient of damage can be detected at 3T in the cortex and thalamus, being more substantial in the thalamus and in PMS.