title: Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation.
abstract: OBJECTIVE
  Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses.
  
  
  OBJECTIVE
  To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation.
  
  
  METHODS
  Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012.
  
  
  METHODS
  Correlation of regional and total brain scores with disease duration.
  
  
  RESULTS
  Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P < .001 for both). The increase in the mean (SD) total brain score from 30.2 (17.3) at baseline to 40.5 (20.6) at follow-up (P = .001) correlated with disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left frontal SI correlated with the degree of spongiosis (r = 0.64, P = .047). Decreased mean diffusivity in the left caudate at follow-up was seen (P < .001). Eight patients demonstrated decreased SI in cortical regions, including the left inferior temporal gyrus and the right lingual gyrus.
  
  
  CONCLUSIONS
  Magnetic resonance images in sCJD show increased extent and degree of SI on DWI that correlates with disease duration and the degree of spongiosis. Although cortical SI may fluctuate, increased basal ganglia SI is a consistent finding and is due to restricted diffusion. Diffusion-weighted imaging in the basal ganglia may provide a noninvasive biomarker in future therapeutic trials.
authors.affiliation: Department of Radiology, University of Utah, Salt Lake City.
authors.forename: Laura
authors.initials: L
authors.lastname: Eisenmenger
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Porter
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Carswell
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Peter
authors.initials: P
authors.lastname: Rudge
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.affiliation: Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, England.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Jäger
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Diseases, University College London Institute of Neurology, London, England.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Hyare
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods / Q000639:trends*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged