Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom, and National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Department of Neurology and Neurosurgery, Institute of Emergency Medicine, Chisinau, Republic of Moldova.
Mov Disord. 2018 Mar;33(3):359-371. doi: 10.1002/mds.27343.
The discovery of genetic links between alpha-synuclein and PD has opened unprecedented opportunities for research into a new group of diseases, now collectively known as synucleinopathies. Autonomic dysfunction, including cardiac sympathetic denervation, has been reported in familial forms of synucleinopathies that have Lewy bodies at the core of their pathogenesis. SNCA mutations and multiplications, LRRK2 disease with Lewy bodies as well as other common, sporadic forms of idiopathic PD, MSA, pure autonomic failure, and dementia with Lewy bodies have all been associated with dysautonomia. By contrast, in familial cases of parkinsonism without Lewy bodies, such as in PARK2, the autonomic profile remains normal throughout the course of the disease. The degeneration of the central and peripheral autonomic systems in genetic as well as sporadic forms of neurodegenerative synucleinopathies correlates with the accumulation of alpha-synuclein immunoreactive-containing inclusions. Given that dysautonomia has a significant impact on the quality of life of sufferers and autonomic symptoms are generally treatable, a prompt diagnostic testing and treatment should be provided. Moreover, new evidence suggests that autonomic dysfunction can be used as an outcome prediction factor in some forms of synucleinopathies or premotor diagnostic markers that could be used in the future to define further research avenues. In this review, we describe the autonomic dysfunction of genetic synucleinopathies in comparison to the dysautonomia of sporadic forms of alpha-synuclein accumulation and provide the reader with an up-to-date overview of the current understanding in this fast-growing field. © 2018 International Parkinson and Movement Disorder Society.
α-突触核蛋白与 PD 之间遗传联系的发现，为研究一组新的疾病（现在统称为突触核蛋白病）开辟了前所未有的机会。在以路易体为发病核心的突触核蛋白病家族形式中，已报道自主神经功能障碍，包括心脏交感神经去神经支配。SNCA 突变和扩增、伴有路易体的 LRRK2 病以及其他常见的散发性特发性 PD、MSA、单纯自主神经衰竭和路易体痴呆，都与自主神经功能障碍有关。相比之下，在无路易体的家族性帕金森病病例中，如 PARK2，自主神经特征在整个疾病过程中保持正常。遗传和散发性神经退行性突触核蛋白病中中枢和外周自主神经系统的退化与α-突触核蛋白免疫反应性包含物的积累相关。鉴于自主神经功能障碍对患者生活质量有重大影响，且自主神经症状通常可治疗，应提供及时的诊断测试和治疗。此外，新的证据表明，自主神经功能障碍可以作为某些突触核蛋白病的预后预测因素，或作为未来用于定义进一步研究途径的前驱诊断标志物。在这篇综述中，我们将描述遗传突触核蛋白病的自主神经功能障碍与散发性α-突触核蛋白积累的自主神经功能障碍进行比较，并为读者提供该快速发展领域的最新概述。© 2018 国际帕金森病和运动障碍学会。
