Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy
Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy
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DOI：
10.1016/j.nbd.2021.105332
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发表时间：
2021-03-19
影响因子：
6.1
通讯作者：
Doppler, Kathrin
中科院分区：
文献类型：
--
作者：
Brumberg, Joachim;Kuzkina, Anastasia;Doppler, Kathrin
在特发性帕金森病和多系统萎缩患者中可以检测到外周真皮神经纤维中的α-突触核蛋白的病理聚集体。本研究结合皮肤活检染色的p-α-突触核蛋白沉积和放射性核素显像的心脏与[I-123]-间碘苄胍，探讨外周去神经支配在这两种疾病。为此，入组了42例临床诊断为帕金森病或多系统萎缩的患者。所有患者均接受了标准化的临床检查，包括神经系统评价、神经造影和血液样本。从腿的远端和近端、背部和颈部获得皮肤活检，用抗-p-α-突触核蛋白和抗-PGP 9.5进行免疫荧光双标记。所有患者均接受了心肌[I-123]-间碘苄胍造影。在47.6%的帕金森病患者中观察到皮肤p-α-突触核蛋白，主要存在于自主神经结构中。81.0%的多系统萎缩患者有沉积物，多位于躯体感觉纤维。帕金森病患者的[I-123]-间碘苄胍心脏与纵隔比值低于多系统萎缩患者（1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001）。无论诊断如何，在自主神经结构中有p-α-突触核蛋白的患者的摄取低于无p-α-突触核蛋白的患者（1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001）。在躯体感觉纤维中存在p-α-突触核蛋白的罕见帕金森病病例和在自主神经结构中存在沉积物的多系统萎缩患者或两种纤维类型均存在临床重叠特征。总之，这项研究表明，α-突触核蛋白有助于周围神经变性和介导的损害，心脏交感神经元与突触核蛋白病患者。此外，这表明帕金森病和多系统萎缩共享周围神经系统功能障碍的病理生理机制，具有临床重叠。
Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [I-123]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [I-123]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [I-123]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.