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
Neurodegenerative Unit, Biocruces Research Institute, Bilbao, Spain; Neurology Service, Cruces University Hospital, Baracaldo, Biscay, Spain.
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.
Parkinsonism Relat Disord. 2015 Jul;21(7):717-22. doi: 10.1016/j.parkreldis.2015.04.012. Epub 2015 Apr 23.
The objective of this study was to assess the presence of autonomic nervous system dysfunction in PARK2 mutation carriers.
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).
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.
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.
本研究的目的是评估PARK2突变携带者中自主神经系统功能障碍的存在情况。
我们对8名PARK2携带者（年龄：60.1±12.8岁）和13名特发性帕金森病（iPD）患者（年龄：59.2±8.9岁）进行了横断面分析。使用SCOPA-AUT问卷、无创自主神经测试以及去甲肾上腺素和血管加压素水平对体位变化的反应来测量自主神经功能障碍。用间碘苄胍（MIBG）闪烁显像评估心肌交感神经去神经支配情况。在一名PARK2携带者和三名对照病例（两名帕金森病患者和一名非帕金森病受试者）的尸检心外膜组织中进一步研究这种损害。
PARK2突变携带者中自主神经症状和体位性低血压（OH）的患病率低于iPD患者（SCOPA OUT：3.4±4.8对14.7±7.2，p<0.001；OH：三名iPD患者存在，而PARK2突变携带者均无）。其次，与对照组相比，PARK2突变携带者的心肌交感神经去神经支配在MIBG闪烁显像（晚期H/M摄取率：1.52±0.35对1.32±0.25，p<0.05）和尸检组织研究中都较轻。有趣的是，PARK2突变携带者的心外膜组织中没有轴突α-突触核蛋白沉积，而两名帕金森病患者中存在。
我们的研究支持以下观点，即PARK2突变携带者的自主神经系统功能障碍和心肌交感神经去神经支配比iPD患者不那么明显，这表明外周小交感神经纤维的受累是PARK2携带者的一个次要病理特征。
