title: Regional and progressive thinning of the cortical ribbon in Huntington's disease.
abstract: BACKGROUND
  Huntington's disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it.
  
  
  METHODS
  Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods.
  
  
  RESULTS
  Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable.
  
  
  CONCLUSIONS
  The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 02129-4404, USA. rosas@helix.mgh.harvard.edu
authors.forename: H D
authors.initials: HD
authors.lastname: Rosas
authors.forename: A K
authors.initials: AK
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Hersch
authors.forename: M
authors.initials: M
authors.lastname: Glessner
authors.forename: R J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: D H
authors.initials: DH
authors.lastname: Salat
authors.forename: A
authors.initials: A
authors.lastname: van der Kouwe
authors.forename: B G
authors.initials: BG
authors.lastname: Jenkins
authors.forename: A M
authors.initials: AM
authors.lastname: Dale
authors.forename: B
authors.initials: B
authors.lastname: Fischl
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged