We aimed to investigate the regional distribution of grey matter (GM) and white matter (WM) atrophy in patients with relapsing–remitting (RR) MS and their relationship with gender, clinical findings, and T2 lesions.
Methods:
Clinical and magnetic resonance imaging assessments were obtained from 78 patients with RRMS and 88 controls. GM and WM atrophy were estimated using voxel-based morphometry (SPM8).
Results:
Patients with RRMS experienced atrophy of the deep GM nuclei, and several cortical regions mainly located in the fronto-parietal lobes. WM atrophy involved posterior regions of the brain, including the cerebellum and brainstem. Compared with men, affected women showed atrophy of several WM tracts, while gender did not impact GM atrophy. Disease duration > 5 years was associated with atrophy of the thalami and inferior frontal gyrus, while WM atrophy was already prominent in patients with disease duration ≤ 5 years. Expanded Disability Status Scale score > 3.0 was associated with diffuse WM atrophy and basal ganglia and precentral gyrus atrophy. T2 lesions were marginally associated to focal atrophy.
Discussion:
In RRMS, GM and WM atrophy have distinct patterns of regional distribution, with a sparing of GM infratentorial regions. Gender, disease duration and disability affect differently the topography of GM/WM atrophy, while T2 lesions play a modest role.
BarkhofFCalabresiPAMillerDHReingoldSC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol2009; 5: 256–266.
2.
ChardDTGriffinCMRashidW. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler2004; 10: 387–391.
3.
De StefanoNMatthewsPMFilippiM. Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology2003; 60: 1157–1162.
4.
AudoinBZaaraouiWReuterF. Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis. J Neurol Neurosurg Psychiatry2010; 81: 690–695.
5.
RazECercignaniMSbardellaE. Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging. Radiology2010; 257: 448–454.
6.
PrinsterAQuarantelliMLanzilloR. A voxel-based morphometry study of disease severity correlates in relapsing– remitting multiple sclerosis. Mult Scler2010; 16: 45–54.
7.
BodiniBKhaleeliZCercignaniMMillerDHThompsonAJCiccarelliO. Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM. Hum Brain Mapp2009; 30: 2852–2861.
8.
SailerMFischlBSalatD. Focal thinning of the cerebral cortex in multiple sclerosis. Brain2003; 126: 1734–1744.
9.
RiccitelliGRoccaMAPaganiE. Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype. Hum Brain Mapp2011; 32: 1535–1543.
10.
CeccarelliARoccaMAPaganiE. A voxel-based morphometry study of grey matter loss in MS patients with different clinical phenotypes. Neuroimage2008; 42: 315–322.
11.
RiccitelliGRoccaMAFornCColomboBComiGFilippiM. Voxel-wise assessment of the regional distribution of damage in the brains of patients with multiple sclerosis and fatigue. AJNR Am J Neuroradiol201132: 874–879.
12.
PellGSBriellmannRSChanCHPardoeHAbbottDFJacksonGD. Selection of the control group for VBM analysis: influence of covariates, matching and sample size. Neuroimage2008; 41: 1324–1335.
13.
LublinFDReingoldSC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology1996; 46: 907–911.
14.
ChardDTJacksonJSMillerDHWheeler-KingshottCA. Reducing the impact of white matter lesions on automated measures of brain gray and white matter volumes. J Magn Reson Imaging2010; 32: 223–228.
15.
AshburnerJ. A fast diffeomorphic image registration algorithm. Neuroimage2007; 38: 95–113.
16.
RovarisMJudicaECeccarelliA. Absence of diffuse cervical cord tissue damage in early, non-disabling relapsing-remitting MS: a preliminary study. Mult Scler2008; 14: 853–856.
CasanovaRSrikanthRBaerA. Biological parametric mapping: A statistical toolbox for multimodality brain image analysis. Neuroimage2007; 34: 137–143.
19.
CaoJWorsleyKJ. The geometry of correlation fields with an application to functional connectivity of the brain. Ann Appl Prob1999; 9: 1021–1057.
20.
MoriSWanakaSVan ZijlPCMNagae-PoetscherLM. MRI atlas of human white matter. Amsterdam, The Netherlands: Elsevier, 2005.
21.
WakanaSCaprihanAPanzenboeckMM. Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage2007; 36: 630–644.
22.
Tzourio-MazoyerNLandeauBPapathanassiouD. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage2002; 15: 273–289.
23.
BattagliniMJenkinsonMDe StefanoN. Evaluating and reducing the impact of white matter lesions on brain volume measurements. Hum Brain Mapp2011. doi: 10.1002/hbm.2134410.1002/hbm.21344 [Epub ahead of print].
24.
BendfeldtKEggerHNicholsTE. Effect of immunomodulatory medication on regional gray matter loss in relapsing-remitting multiple sclerosis– a longitudinal MRI study. Brain Res2010; 1325: 174–182.
25.
PrinsterAQuarantelliMOreficeG. Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study. Neuroimage2006; 29: 859–867.
26.
MesarosSRovarisMPaganiE. A magnetic resonance imaging voxel-based morphometry study of regional gray matter atrophy in patients with benign multiple sclerosis. Arch Neurol2008; 65: 1223–1230.
27.
RamasamyDPBenedictRHCoxJL. Extent of cerebellum, subcortical and cortical atrophy in patients with MS: a case-control study. J Neurol Sci2009; 282: 47–54.
28.
KutzelniggAFaber-RodJCBauerJ. Widespread demyelination in the cerebellar cortex in multiple sclerosis. Brain Pathol2007; 17: 38–44.
29.
PozzilliCTomassiniVMarinelliFPaolilloAGasperiniCBastianelloS. ‘Gender gap’ in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol2003; 10: 95–97.
30.
AntulovRWeinstock-GuttmanBCoxJL. Gender-related differences in MS: a study of conventional and nonconventional MRI measures. Mult Scler2009; 15: 345–354.
31.
BrownellBHughesJT. The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry1962; 25: 315–320.
32.
CifelliAArridgeMJezzardPEsiriMMPalaceJMatthewsPM. Thalamic neurodegeneration in multiple sclerosis. Ann Neurol2002; 52: 650–653.
33.
WylezinskaMCifelliAJezzardPPalaceJAlecciMMatthewsPM. Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology2003; 60: 1949–1954.
34.
HenryRGShiehMOkudaDTEvangelistaAGorno-TempiniMLPelletierD. Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry2008; 79: 1236–1244.
35.
SepulcreJSastre-GarrigaJCercignaniMIngleGTMillerDHThompsonAJ. Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. Arch Neurol2006; 63: 1175–1180.
36.
AudoinBDaviesGRFiniskuLChardDTThompsonAJMillerDH. Localization of grey matter atrophy in early RRMS: A longitudinal study. J Neurol2006; 253: 1495–1501.
37.
MesarosSRoccaMAAbsintaM. Evidence of thalamic gray matter loss in pediatric multiple sclerosis. Neurology2008; 70: 1107–1112.
38.
RoccaMAMesarosSPaganiESormaniMPComiGFilippiM. Thalamic damage and long-term progression of disability in multiple sclerosis. Radiology2010; 257: 463–469.
