Beatriz Tijero1, Iñigo Gabilondo1, Elena Lezcano2, Nuria Teran-Villagrá3, Verónica Llorens4, Javier Ruiz-Martinez5, Jose Felix Marti-Masso6, M Carmona7, Maria Rosario Luquin7, Koldo Berganzo1, Ivan Fernandez8, Manuel Fernandez2, Juan José Zarranz2, Juan Carlos Gómez-Esteban9. 1. Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain. 2. 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. 3. Pathology Service, University Hospital Marques de Valdecilla, Santander, Cantabria, Spain. 4. Nuclear Medicine Service Cruces University Hospital, Baracaldo, Spain. 5. Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain; Department of Neurology, University Hospital Donostia, San Sebastian, Spain. 6. 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. 7. Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. 8. Pathology Service, Hospital Universitario de Araba-Txagorritxu, Vitoria, Spain. 9. 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.
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 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. 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.
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 PDpatients 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 PDpatients. 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.