Age at disease onset influences gray matter and white matter damage in adult multiple sclerosis patients
Elisabetta Pagani1, Maria Assunta Rocca1,2, Laura Vacchi1, Bruno Colombo2, Mariaemma Rodegher2, Lucia Moiola2, Angelo Ghezzi3, Giancarlo Comi2, Andrea Falini4, and Massimo Filippi1,2

1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3Multiple Sclerosis Study Center, Hospital of Gallarate, Gallarate, Italy, 4Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Synopsis

Aim of the study was to explore the extent and distribution of brain gray matter (GM) atrophy and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients according to their age at disease onset. High-resolution T1-weighted and diffusion tensor MRI scans were acquired from 58 pediatric-onset MS patients, 58 age-matched and 58 disease duration-matched adult-onset MS patients, and 58 healthy controls. The distribution of atrophy and microstructural WM damage were assessed using voxel-wise approaches. Neurodegenerative and inflammatory-demyelinating processes seemed less pronounced in pediatric-onset MS patients. However, with increasing disease duration, an accelerated normal appearing WM damage occurred.

Background

Age at disease onset may influence clinical status (level and time to reach fixed disability) during adulthood. Maturational effects and the presence of different pathophysiological mechanisms could contribute to explain clinical differences between multiple sclerosis (MS) patients with pediatric and adult onset.

Purpose

To explore the extent and distribution of brain gray matter (GM) atrophy and white matter (WM) microstructural abnormalities in adult MS patients according to their age at disease onset.

Methods

High-resolution T1-weighted and diffusion tensor (DT) MRI scans were acquired from 58 pediatric-onset (PO) MS patients, 58 age-matched (AOA) and 58 disease duration-matched (AODD) adult-onset MS patients, and 58 healthy controls. The distribution of GM and WM atrophy was assessed using SPM12 and Voxel Based Morphometry (1). Tract Based Spatial Statistics (TBSS) (2) was applied for voxel-wise analysis of DT-derived maps. Between-group comparisons were adjusted for age or disease duration, as appropriate. Correlations with age at disease onset were analyzed.

Results

Compared to healthy controls, MS patients had the expected patterns of regional GM atrophy and WM DT MRI abnormalities. Compared to PO-MS, AOA patient showed a reduced fractional anisotropy (FA) in the main supratentorial WM tracts (corpus callosum, cingulum, corona radiata, internal and external capsulae, posterior thalamic radiation), bilaterally, corona radiata, external capsulae, posterior thalamic radiation) (Figure 1). Compared to AODD, PO-MS had a reduced FA in the previous WM tracts (Figure 2). Compared to PO-MS, AOA patients had a widespread pattern of regional GM atrophy (Figure 3), whereas no difference was found between PO-MS and AODD patients.

Conclusions

This multiparametric MRI study suggests that different pathological processes may operate in MS patients according to their age at disease onset. Compared to AOA, PO-MS patients have less extensive GM atrophy and less severe normal appearing WM damage, suggesting that neurodegenerative and inflammatory-demyelinating processes could be less pronounced in these patients. However, with increasing disease duration, an accelerated normal appearing WM damage seems to occur in these patients, which suggest an impaired reserve for structural plasticity over the long term.

Acknowledgements

Partially supported by a grant from Italian Ministry of Health (GR-2009-1529671).

References

1) Ashburner J. Computational anatomy with the SPM software. Magn Reson Imaging. 2009;27(8):1163-74.

2) Smith SM, Jenkinson M, Johansen-Berg H, et al. Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. NeuroImage, 2006;31:1487-1505.

Figures

Figure 1. TBSS results. In red, voxels of the WM skeleton where the FA index was found significantly decreased in AOA-MS vs PO-MS patients (disease duration-adjusted analysis).

Figure 2. TBSS results. In red, voxels of the WM skeleton where the FA index was found significantly decreased in PO-MS vs AODD-MS patients (age-adjusted analysis).

Figure 3. Voxel Based Morphometry results. In yellow, voxels of the GM with significantly decreased volume in PO-MS vs AOA-MS (age-adjusted analysis.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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