title: Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations.
abstract: OBJECTIVE
  The objective of this study was to assess the presence of autonomic nervous system dysfunction in PARK2 mutation carriers.
  
  
  METHODS
  We performed a cross-sectional analysis of 8 PARK2 carriers (age: 60.1 ± 12.8 years) and 13 individuals with idiopathic PD (iPD) (age: 59.2 ± 8.9 years). Autonomic dysfunction was measured using the SCOPA-AUT questionnaire, non-invasive autonomic tests and responses of noradrenaline and vasopressin levels to postural changes. Myocardial sympathetic denervation was assessed with metaiodobenzylguanidine (MIBG) scintigraphy. This damage was further investigated in postmortem epicardial tissue of one PARK2 carrier and three control cases (two PD patients and one subject without PD).
  
  
  RESULTS
  The prevalence of autonomic symptoms and orthostatic hypotension (OH) was lower in PARK2 mutation carriers than in iPD patients (SCOPA OUT: 3.4 ± 4.8 vs. 14.7 ± 7.2, p < 0.001; OH: present in three iPD patients but none of the PARK2 mutation carriers). Second, sympathetic myocardial denervation was less severe in PARK2 mutation carriers compared to controls, both in MIBG scintigraphy (late H/M uptake ratio: 1.52 ± 0.35 vs. 1.32 ± 0.25 p < 0.05) and in postmortem tissue study. Interestingly, axonal alpha-synuclein deposits were absent in epicardial tissue of the PARK2 mutation carrier while they were present in the two PD patients.
  
  
  CONCLUSIONS
  Our study supports the view that autonomic nervous system dysfunction and myocardial sympathetic denervation are less pronounced in PARK2 mutation carriers than in individuals with iPD, suggesting that the involvement of small peripheral sympathetic nerve fibers is a minor pathological hallmark in PARK2 carriers.
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tijero
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Gabilondo
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain; Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Lezcano
authors.affiliation: Pathology Service, University Hospital Marques de Valdecilla, Santander, Cantabria, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Teran-Villagrá
authors.affiliation: Nuclear Medicine Service Cruces University Hospital, Baracaldo, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Llorens
authors.affiliation: Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain; Department of Neurology, University Hospital Donostia, San Sebastian, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martinez
authors.affiliation: Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain; Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain; Department of Neurology, University Hospital Donostia, San Sebastian, Spain.
authors.forename: Jose Felix
authors.initials: JF
authors.lastname: Marti-Masso
authors.affiliation: Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Carmona
authors.affiliation: Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Maria Rosario
authors.initials: MR
authors.lastname: Luquin
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain.
authors.forename: Koldo
authors.initials: K
authors.lastname: Berganzo
authors.affiliation: Pathology Service, Hospital Universitario de Araba-Txagorritxu, Vitoria, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain; Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fernandez
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain; Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Zarranz
authors.affiliation: Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain; Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain. Electronic address: juancarlos.gomezesteban@osakidetza.net.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gómez-Esteban
mesh_terms: D000328:Adult; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Autonomic function; Autonomic tests; PARK2 mutation; Parkinson's disease