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
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Ashburner J. Computational anatomy with the SPM software. Magn Reson
Imaging. 2009;27(8):1163-74.
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Smith SM, Jenkinson M, Johansen-Berg H, et
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Voxelwise analysis of multi-subject diffusion data. NeuroImage,
2006;31:1487-1505.