title: White matter involvement in sporadic Creutzfeldt-Jakob disease.
abstract: Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss.
authors.affiliation: 1 Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143, USA CaverzasiE@smh.ca.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Caverzasi
authors.affiliation: 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mandelli
authors.affiliation: 3 Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA 4 Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.affiliation: 5 Neuroradiology Division, Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Hess
authors.affiliation: 6 Brain MRI 3T Mondino Research Center, C. Mondino National Neurological Institute, Pavia 27100, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitali
authors.affiliation: 1 Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Nico
authors.initials: N
authors.lastname: Papinutto
authors.affiliation: 3 Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA 4 Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Abby
authors.initials: A
authors.lastname: Oehler
authors.affiliation: 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: 1 Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: 7 Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bastianello
authors.affiliation: 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind
authors.affiliation: 1 Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA 8 Bioengineering Graduate Group, University of California San Francisco, San Francisco, CA 94143, USA 9 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D059906:Neuroimaging; D066127:White Matter / Q000473:pathology*
keywords: CJD; DTI; gliosis; mean diffusivity; microglia