title: Multimodal imaging evidence of pathology-mediated disease distribution in corticobasal syndrome.
abstract: OBJECTIVE
  To use multimodal neuroimaging to evaluate the influence of heterogeneous underlying pathology in corticobasal syndrome (CBS) on the neuroanatomical distribution of disease.
  
  
  METHODS
  We performed a retrospective evaluation of 35 patients with CBS with T1-weighted MRI, diffusion tensor imaging, and neuropathologic, genetic, or CSF evidence of underlying pathology. Patients were assigned to 2 groups: those with evidence of Alzheimer pathology (CBS-AD) and those without Alzheimer pathology (CBS-non-AD). Group comparisons of CBS-AD and CBS-non-AD assessed clinical features, gray matter (GM) cortical thickness, and white matter (WM) fractional anisotropy.
  
  
  RESULTS
  CBS-AD was found in 34% (n = 12) and CBS-non-AD in 66% (n = 23) of CBS patients. Clinical evaluations revealed that CBS-non-AD had a higher frequency of asymmetric rigidity compared to CBS-AD, but groups otherwise did not differ in dementia severity, impairments in cognition, or rates of extrapyramidal symptoms. We found frontoparietal GM and WM disease in each group compared to healthy, demographically comparable controls, as well as multimodal neuroimaging evidence of a double dissociation: CBS-non-AD had WM disease in the corpus callosum, corticospinal tract, and superior longitudinal fasciculus relative to CBS-AD, and CBS-AD had reduced temporoparietal GM relative to CBS-non-AD, including the precuneus and posterior cingulate.
  
  
  CONCLUSIONS
  Patients with CBS have a pathology-mediated dissociation of GM and WM disease. Multimodality neuroimaging may be useful for improving in vivo pathologic diagnosis of CBS.
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. mcmillac@mail.med.upenn.edu.
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Clara
authors.initials: C
authors.lastname: Boyd
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Gross
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Weinstein
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Kim
authors.initials: K
authors.lastname: Firn
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Katya
authors.initials: K
authors.lastname: Rascovsky
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Leslie
authors.initials: L
authors.lastname: Shaw
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: From the Department of Neurology (C.T.M., C.B., R.G.G., J.W., K.F., K.R., D.A.W., D.J.I., M.G.) and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine (J.B.T., L.S., D.J.I., E.B.L., J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D009929:Organ Size; D012189:Retrospective Studies; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology