Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations

• Published in: Parkinsonism & related disorders Vol. 21; no. 7; pp. 717 - 722
• Main Authors: Tijero, Beatriz, Gabilondo, Iñigo, Lezcano, Elena, Teran-Villagrá, Nuria, Llorens, Verónica, Ruiz-Martinez, Javier, Marti-Masso, Jose Felix, Carmona, M, Luquin, Maria Rosario, Berganzo, Koldo, Fernandez, Ivan, Fernandez, Manuel, Zarranz, Juan José, Gómez-Esteban, Juan Carlos
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2015
• Subjects: Adult; Aged; Autonomic function; Autonomic Nervous System Diseases - diagnosis; Autonomic Nervous System Diseases - epidemiology; Autonomic Nervous System Diseases - genetics; Autonomic tests; Cross-Sectional Studies; Female; Heterozygote; Humans; Male; Middle Aged; Mutation - genetics; Neurology; PARK2 mutation; Parkinson's disease; Parkinsonian Disorders - diagnosis; Parkinsonian Disorders - epidemiology; Parkinsonian Disorders - genetics; Ubiquitin-Protein Ligases - genetics; Autonomic function; PARK2 mutation; Autonomic tests; Parkinson's disease
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2015.04.012

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.