Gray Matter Involvement in Radiologically Isolated Syndrome

Abstract

The unanticipated magnetic resonance imaging (MRI) detection in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis has recently been named as radiologically isolated syndrome (RIS). The pathophysiological processes of RIS remain largely unknown and questions as to whether gray matter alterations actually occur in this entity are yet to be investigated in more detail. By means of a 3 T multimodal MRI approach, we searched for cortical and deep gray matter changes in a cohort of RIS patients. Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median disease duration from symptom onset = 12 months), and 17 healthy controls underwent MRI and neuropsychological testing. Normalized deep gray matter volumes and regional cortical thickness were assessed using FreeSurfer. SIENAX was used to obtain normalized global and cortical brain volumes. Voxelwise morphometry analysis was performed by using SPM8 software to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Although no differences were observed between CIS and healthy controls groups, RIS patients showed significantly lower normalized cortical volume (673 ± 27.07 vs 641 ± 35.88 [cm3 × 103, Tukey P test = 0.009) and mean thalamic volume (0.0051 ± 0.4 vs 0.0046 ± 0.4 mm, P = 0.014) compared with healthy controls. RIS patients also showed significant thinning in a number of cortical areas, that were primarily distributed in frontal and temporal lobes (P < 0.05, uncorrected). Strong correlations were observed between T2-white matter lesion volume and regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data suggest that white matter lesions on T2-weighted images are not the only hallmark of RIS. Future longitudinal studies with larger samples are warranted to better clarify the effect of RIS-related white matter lesions on gray matter tissue.

Radiologically isolated syndrome: An update on a rare entity

“…Diffusion tensor imaging studies, regardless of the analysis method used to determine fractional anisotropy or mean diffusivity measures, have revealed that RIS patients do show altered microstructural white matter integrity with respect to controls but only correspondence of lesions. 29,30 Taken together, these studies strongly suggest that occult microstructural normal-appearing white matter damage is not significantly present outside visible T2 lesions in RIS, suggesting that RIS patients might have experienced more efficient reparative mechanisms after white matter injury.…”

“…25,30 In addition, we have recently found significant thinning in a number of cortical areas primarily distributed in frontal and temporal lobes, as well as cingulate cortex. 30 Remarkably, we did not observe cortical thickness in those brain regions that have been shown to play a critical role in motor function and physical dysfunction (precentral gyrus, sensorimotor cortex, and cerebellum), which may help explain why RIS patients maintain motor functions. 30 In contrast to our results, Azevedo et al 25 found only a limited area of thinning in the right superior and inferior parietal gyri.…”

Imaging as an Outcome Measure in Multiple Sclerosis

“…Gray matter atrophy is found in a gradient with increasing severity in clinically isolated syndrome, RRMS, and SPMS (as compared with healthy controls), while white matter atrophy appears to be relatively constant of the disease course. Mechanisms of direct injury, as well as antegrade and retrograde axonal degeneration, has been hypothesized for the gray matter in MS-even in radiologically isolated syndrome gray matter volume is reduced [33]. Gray matter atrophy demonstrates stronger correlations with cognitive function [34,35].…”

Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI

“…There is a growing amount of evidence suggesting that RIS and MS patients share both nonmotor clinical features [ 2 – 5 ] and quantitative brain tissue damage. [ 6 – 12 ] Accordingly, approximately one-third of RIS subjects, especially those with spinal cord involvement, will present a future demyelinating event within 5 years after diagnosis. [ 13 ] However, to date it remains largely unknown whether there is in RIS brain damage beyond visible T2 white matter lesions.…”