title: Subcortical deep gray matter pathology in patients with multiple sclerosis is associated with white matter lesion burden and atrophy but not with cortical atrophy: a diffusion tensor MRI study.
abstract: OBJECTIVE
  The association between subcortical deep gray matter, white matter, and cortical pathology is not well understood in MS. The aim of this study was to use DTI to investigate the subcortical deep gray matter alterations and their relationship with lesion burden, white matter, and cortical atrophy in patients with MS and healthy control patients.
  
  
  METHODS
  A total of 210 patients with relapsing-remitting MS, 75 patients with progressive MS, and 110 healthy control patients were included in the study. DTI metrics in whole brain, normal-appearing white matter, normal-appearing gray matter, and subcortical deep gray matter structures were compared. The association between DTI metrics of the subcortical deep gray matter structures with lesion burden, normalized white matter volume, and normalized cortical volume was investigated.
  
  
  RESULTS
  DTI measures were significantly different in whole brain, normal-appearing white matter, and normal-appearing gray matter among the groups (P < .01). Significant differences in DTI diffusivity of total subcortical deep gray matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity of total subcortical deep gray matter was significantly associated with normalized white matter volume (P < .001) and normalized cortical volume (P = .033) in healthy control patients. In both relapsing and progressive MS groups, the DTI subcortical deep gray matter measures were associated with the lesion burden and with normalized white matter volume (P < .001), but not with normalized cortical volume.
  
  
  CONCLUSIONS
  These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.)Department GF Ingrassia, Section of Neurosciences (R.C., F.P.), University of Catania, Catania, Italy.
authors: R
authors: R
authors: Cappellani
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: N
authors: N
authors: Bergsland
authors: Jacobs Neurological Institute, Department of Neurology (B.W.-G., R.Z.), State University of New York, Buffalo, New York.
authors: B
authors: B
authors: Weinstock-Guttman
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: C
authors: C
authors: Kennedy
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: E
authors: E
authors: Carl
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: D P
authors: DP
authors: Ramasamy
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: J
authors: J
authors: Hagemeier
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.).
authors: M G
authors: MG
authors: Dwyer
authors: Department GF Ingrassia, Section of Neurosciences (R.C., F.P.), University of Catania, Catania, Italy.
authors: F
authors: F
authors: Patti
authors: From the Buffalo Neuroimaging Analysis Center (R.C., N.B., C.K., E.C., D.P.R., J.H., M.G.D., R.Z.)Jacobs Neurological Institute, Department of Neurology (B.W.-G., R.Z.), State University of New York, Buffalo, New York rzivadinov@bnac.net.
authors: R
authors: R
authors: Zivadinov
mesh_terms: D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D015588:Observer Variation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology*