title: Clinicopathological correlations in corticobasal degeneration.
abstract: OBJECTIVE
  To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology.
  
  
  METHODS
  We reviewed clinical and magnetic resonance imaging data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n = 18) or clinical CBS at first presentation with known histopathology (n = 40). Atrophy patterns were compared using voxel-based morphometry.
  
  
  RESULTS
  CBD was associated with 4 clinical syndromes: progressive nonfluent aphasia (n = 5), behavioral variant frontotemporal dementia (n = 5), executive-motor (n = 7), and posterior cortical atrophy (n = 1). Behavioral or cognitive problems were the initial symptoms in 15 of 18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and perirolandic cortex, striatum, and brainstem (p < 0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p < 0.001 uncorrected).
  
  
  CONCLUSIONS
  Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia, symptoms dominate early stage disease. CBS is driven by medial perirolandic dysfunction, but this anatomy is not specific to a single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified.
authors.affiliation: Memory and Aging Center, University of California San Francisco, San Francisco, CA 94143, USA. suzeelee@memory.ucsf.edu
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: Mary Catherine
authors.initials: MC
authors.lastname: Mayo
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Wilson
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Huang
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Growdon
authors.forename: Jung Y
authors.initials: JY
authors.lastname: Jang
authors.forename: Manu
authors.initials: M
authors.lastname: Sidhu
authors.forename: Tricia M
authors.initials: TM
authors.lastname: See
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001479:Basal Ganglia / Q000473:pathology* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D009483:Neuropsychological Tests; D013577:Syndrome