title: Network correlates of disease severity in multiple system atrophy.
abstract: OBJECTIVE
  Multiple system atrophy (MSA), the most common of the atypical parkinsonian disorders, is characterized by the presence of an abnormal spatial covariance pattern in resting state metabolic brain images from patients with this disease. Nonetheless, the potential utility of this pattern as a MSA biomarker is contingent upon its specificity for this disorder and its relationship to clinical disability in individual patients.
  
  
  METHODS
  We used [(18)F]fluorodeoxyglucose PET to study 33 patients with MSA, 20 age- and severity-matched patients with idiopathic Parkinson disease (PD), and 15 healthy volunteers. For each subject, we computed the expression of the previously characterized metabolic covariance patterns for MSA and PD (termed MSARP and PDRP, respectively) on a prospective single-case basis. The resulting network values for the individual patients were correlated with clinical motor ratings and disease duration.
  
  
  RESULTS
  In the MSA group, disease-related pattern (MSARP) values were elevated relative to the control and PD groups (p < 0.001 for both comparisons). In this group, MSARP values correlated with clinical ratings of motor disability (r = 0.57, p = 0.0008) and with disease duration (r = -0.376, p = 0.03). By contrast, MSARP expression in the PD group did not differ from control values (p = 1.0). In this group, motor ratings correlated with PDRP (r = 0.60, p = 0.006) but not with MSARP values (p = 0.88).
  
  
  CONCLUSIONS
  MSA is associated with elevated expression of a specific disease-related metabolic pattern. Moreover, differences in the expression of this pattern in patients with MSA correlate with clinical disability. The findings suggest that the MSARP may be a useful biomarker in trials of new therapies for this disorder.
authors.affiliation: Stanford University Medical Center, Stanford, CA, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Poston
authors.forename: C C
authors.initials: CC
authors.lastname: Tang
authors.forename: T
authors.initials: T
authors.lastname: Eckert
authors.forename: V
authors.initials: V
authors.lastname: Dhawan
authors.forename: S
authors.initials: S
authors.lastname: Frucht
authors.forename: J-P
authors.initials: JP
authors.lastname: Vonsattel
authors.forename: S
authors.initials: S
authors.lastname: Fahn
authors.forename: D
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D059907:Functional Neuroimaging / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18