title: Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease.
abstract: Attention has been drawn to cardiac sympathetic denervation in Parkinson's disease (PD) based on clinical studies using [123I] metaiodobenzylguanidine scintigraphy; however, the histologic correlates and time course of cardiac sympathetic denervation are poorly understood. To address these issues, we used tyrosine hydroxylase (TH) immunohistochemistry to detect cardiac sympathetic nerve fibers in the epicardium of 4 normal controls, 11 cases with incidental Lewy bodies (iLBs), and 14 cases of PD. Cardiac sympathetic innervation was significantly less in PD than in normal controls and cases with iLBs (P < 0.05). There was also a decrease in TH-immunoreactive fibers in iLB cases compared to normal controls (P < 0.01). TH-immunoreactive fibers correlated with the PD stage (r = -0.75, P < 0.001), as well as with Hoehn & Yahr clinical stage (r = -0.61, P < 0.001), and disease duration (r = -0.63, P < 0.001). Immunohistochemistry for alpha-synuclein showed neurites in epicardium in PD and iLB cases, but not in normal controls. The density of alpha-synuclein neurites correlated with Braak PD stage (r = 0.38, P < 0.05), Hoehn & Yahr clinical stage (r = 0.44, P < 0.05), and disease duration (r = 0.42, P < 0.05). This study demonstrates that cardiac sympathetic degeneration and alpha-synuclein pathology is present in presymptomatic phase of PD, and that both increase with disease duration and severity.
authors.affiliation: Department of Pathology (Neuropathology), Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Fujishiro
authors.forename: Roberta
authors.initials: R
authors.lastname: Frigerio
authors.forename: Melinda
authors.initials: M
authors.lastname: Burnett
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Klos
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
authors.forename: Anthony
authors.initials: A
authors.lastname: Delledonne
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.forename: J Eric
authors.initials: JE
authors.lastname: Ahlskog
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006321:Heart / Q000294:innervation*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000175:diagnosis / Q000473:pathology; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology; D016501:Neurites / Q000473:pathology; D010300:Parkinson Disease / Q000175:diagnosis / Q000473:pathology*; D010496:Pericardium / Q000294:innervation / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013564:Sympathetic Nervous System / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D051844:alpha-Synuclein / Q000032:analysis
chemical_list: D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase