Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations Beatriz Tijero a, b ,I ~ nigo Gabilondo a, b , Elena Lezcano a, b, c , Nuria Teran-Villagr  a d , Ver  onica Llorens e , Javier Ruiz-Martinez f, g , Jose Felix Marti-Masso c, f, g , M. Carmona h , Maria Rosario Luquin h , Koldo Berganzo a, b , Ivan Fernandez i , Manuel Fernandez a, b, c , Juan Jos  e Zarranz a, b, c , Juan Carlos G  omez-Esteban a, b, c, * a Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain b Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain c Department of Neurosciences, School of Medicine and Dentistry University of the Basque Country, Leioa, Biscay, Spain d Pathology Service, University Hospital Marques de Valdecilla, Santander, Cantabria, Spain e Nuclear Medicine Service Cruces University Hospital, Baracaldo, Spain f Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain g Department of Neurology, University Hospital Donostia, San Sebastian, Spain h Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain i Pathology Service, Hospital Universitario de Araba-Txagorritxu, Vitoria, Spain article info Article history: Received 8 October 2014 Received in revised form 3 April 2015 Accepted 14 April 2015 Keywords: Parkinson's disease Autonomic function PARK2 mutation Autonomic tests abstract Background and objectives: The objective of this study was to assess the presence of autonomic nervous system dysfunction in PARK2 mutation carriers. Patients and 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 denerva- tion 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. Interpretation: 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. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Mutations in the PARK2 gene explain up to half of the cases with recessively inherited Parkinson's disease (PD), and 15% of sporadic PD with onset before 45 years of age [1]. Compared to idiopathic PD (iPD), patients with PARK2 gene mutations have significantly earlier * Corresponding author. Servicio de Neurología, Hospital de Cruces, Plaza de Cruces s/n. Baracaldo, Vizcaya, CP 48903, Spain. E-mail address: juancarlos.gomezesteban@osakidetza.net (J.C. G omez-Esteban). Contents lists available at ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis http://dx.doi.org/10.1016/j.parkreldis.2015.04.012 1353-8020/© 2015 Elsevier Ltd. All rights reserved. Parkinsonism and Related Disorders 21 (2015) 717e722