title: A disease-specific metabolic brain network associated with corticobasal degeneration.
abstract: Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼ 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes.
authors.affiliation: 1 Centre for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Niethammer
authors.affiliation: 1 Centre for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Tang
authors.affiliation: 1 Centre for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Feigin
authors.affiliation: 1 Centre for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: 2 Department of Neurology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Heinen
authors.affiliation: 3 Department of Neurology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.affiliation: 3 Department of Neurology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Amtage
authors.affiliation: 4 Parkinson's Disease and Movement Disorders Centre, Albany Medical Centre, Albany, NY 12208, USA.
authors.forename: Era
authors.initials: E
authors.lastname: Hanspal
authors.affiliation: 5 The New York Brain Bank, Columbia Presbyterian Medical Centre, New York, NY 10032, USA.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: 6 Department of Neurology and Neurological Sciences, Stanford University Medical Centre, Stanford, CA 94305, USA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Poston
authors.affiliation: 7 Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: 2 Department of Neurology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Klaus L
authors.initials: KL
authors.lastname: Leenders
authors.affiliation: 1 Centre for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA david1@nshs.edu.
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001480:Basal Ganglia Diseases / Q000145:classification / Q000175:diagnosis / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D054022:Cerebrum / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000145:classification / Q000175:diagnosis / Q000378:metabolism; D009415:Nerve Net / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000145:classification / Q000175:diagnosis / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013494:Supranuclear Palsy, Progressive / Q000145:classification / Q000175:diagnosis / Q000378:metabolism
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: FDG PET; brain networks; corticobasal degeneration; differential diagnosis; glucose metabolism