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Evidence of thalamic gray matter loss in pediatric multiple sclerosis

From the Neuroimaging Research Unit (S.M., M.A.R., M.A., M.F.), Department of Neurology (M.A.R., M.A., L.M., G.C., M.F.), Scientific Institute and University Ospedale San Raffaele, Milan; Multiple Sclerosis Center (A.G.), Ospedale di Gallarate; Neurological Institute ‘Carlo Besta' (N.M.), Milan; and Fondazione Istituto Neurologico Casimiro Mondino (P.V.), Pavia, Italy.

Address correspondence and reprint requests to Dr. Massimo Filippi, Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Via Olgettina 60, 20132 Milan, Italy filippi.massimo{at}hsr.it

Objective: We used voxel-based morphometry (VBM) to assess the pattern of regional gray matter (GM) loss in patients with pediatric multiple sclerosis (MS) and its relation with the Expanded Disability Status Scale (EDSS) score, disease duration, and the extent of T2 lesion load (LL).

Methods: From 28 patients with pediatric relapsing-remitting MS (16 girls; mean age = 14.4 years, range = 7 to 16 years) and 21 matched controls, dual-echo and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo sequences were acquired. T2 LL was measured using a local thresholding segmentation technique. Data were analyzed using an optimized VBM analysis and statistical parametric mapping.

Results: In pediatric patients with MS, mean brain T2 LL was 7.8 mL ± 11.3. Intracranial volume did not differ between patients and controls. Compared to controls, patients with pediatric MS had significant GM loss in the thalamus, bilaterally, which was significantly correlated with T2 LL (r = –0.80 for the right thalamus, r = –0.74 for the left thalamus, p < 0.05, corrected for multiple comparisons). No correlation was found between thalamic GM loss, disease duration, and disability.

Conclusions: In patients with pediatric multiple sclerosis (MS), differently from what happens in adult-onset MS, gray matter (GM) atrophy seems to involve the thalamus only, with sparing of the cortex and other deep GM nuclei. The correlation found between atrophy and T2 lesion load suggests transsynaptic and Wallerian degenerations as the most likely substrate of tissue loss in the thalamus of these patients.

GLOSSARY: DT = diffusion tensor; EDSS = Expanded Disability Status Scale; FA = flip angle; FOV = field of view; LL = lesion load; GM = gray matter; ICV = intracranial volume; MP-RAGE = magnetization prepared rapid acquisition gradient echo;MS = multiple sclerosis; MT = magnetization transfer; NAWM = normal-appearing white matter; NBV = normalized brain volume; NGM = normalized GM; RR = relapsing-remitting; TE = echo time; TR = repetition time; TSE = turbo spin-echo; VBM = voxel-based morphometry.

Editorial, page 1065

e-Pub ahead of print on February 13, 2008, at www.neurology.org.

Supported by a grant from the Fondazione Mariani (contract R-07-62). S.M. was supported by a Fellowship of the European Neurological Society (ENS).

Disclosure: The authors report no conflicts of interest.

Received June 26, 2007. Accepted in final form September 10, 2007.

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				S. Mesaros, M. Rovaris, E. Pagani, A. Pulizzi, D. Caputo, A. Ghezzi, A. Bertolotto, R. Capra, M. Falautano, V. Martinelli, et al. A Magnetic Resonance Imaging Voxel-Based Morphometry Study of Regional Gray Matter Atrophy in Patients With Benign Multiple Sclerosis Arch Neurol, September 1, 2008; 65(9): 1223 - 1230. [Abstract] [Full Text] [PDF]

				B. L. Banwell and J. G. Sled Starting early: MRI evidence of gray matter atrophy in children with multiple sclerosis Neurology, March 25, 2008; 70(13_Part_2): 1065 - 1066. [Full Text] [PDF]