title: 2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.
abstract: The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using11C-hydroxyephedrine (11C-HED) PET and determine the denervation rate over 2 y.
  
  
  
  We obtained 62 cardiac11C-HED PET scans in 39 patients (30 men and 9 women; mean age ± SD, 61.9 ± 5.9 y), including 23 patients with follow-up scans at 2 y. We derived11C-HED retention indices (RIs; mL of blood/min/mL of tissue) reflecting nerve density and integrity for 480 left ventricular (LV) sectors. We compared IPD patients with 33 healthy controls using z score analysis; RI values ≤ 2.5 SDs were considered abnormal. We expressed global and regional LV denervation as the percentage extent of z score severity and severity-extent product (SEP) on 9-segment bullseye maps and decline in cardiac sympathetic innervation as the 2-y difference in SEP (diff-SEP).
  
  
  
  Baseline11C-HED PET in the 39 IPD patients revealed an RI mean of 0.052 ± 0.022 mL of blood/min/mL of tissue. In comparison with data from normal controls, 12 patients had normal11C-HED PET, 5 showed mild denervation (percentage extent < 30%), and 22 had moderate to severe denervation (percentage extent > 30%, z score ≤ 2.5 SD). In the 23 paired PET scans, worsening cardiac denervation (global diff-SEP > 9) occurred in 14 of 23 (60.9%) patients over 2 y, including percentage LV abnormality (59% increasing to 66%), z-severity (-2.4 down to -2.5), and SEP (-195 to -227) (P = 0.0062). We found a mean annual decline of 4.6% ± 5.6 (maximum, 13%) in11C-HED retention from a baseline global RI mean of 0.0481 ± 0.0218 to 0.0432 ± 0.0220 (P = 0.0009). At baseline, 5 patients with normal uptake had no interval change; 3 with mild denervation developed interval decline in lateral and inferior segments (diff-SEP -82 to -99) compared with anterior and septal segments (-65 to -79), whereas the reverse pattern occurred in 15 patients with severe baseline denervation.
  
  
  
  Progressive decline in cardiac sympathetic neural integrity in IPD patients occurs at a modest rate over 2 y on11C-HED scans with marked heterogeneity and a regional pattern of involvement and decline.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan kakit@med.umich.edu.|VA Ann Arbor Healthcare System, GRECC, Ann Arbor, Michigan.
authors.forename: Ka Kit
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: David M
authors.initials: DM
authors.lastname: Raffel
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan.|VA Ann Arbor Healthcare System, GRECC, Ann Arbor, Michigan.|Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, Ann Arbor, Michigan.|University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, Michigan.
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Altinok
authors.affiliation: Department of Neurology, University of Michigan (retired), Ann Arbor, Michigan; and.
authors.forename: Sid
authors.initials: S
authors.lastname: Gilman
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan.|Department of Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D018450:Disease Progression; D004809:Ephedrine / Q000031:analogs & derivatives*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D004809:Ephedrine
keywords: 11C-hydroxyephedrine PET; Parkinson disease; autonomic nervous system; cardiac sympathetic denervation