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帕金森病中α-突触核蛋白包涵体的体内胃部检测

In vivo gastric detection of α-synuclein inclusions in Parkinson's disease.

作者信息

Sánchez-Ferro Álvaro, Rábano Alberto, Catalán María José, Rodríguez-Valcárcel Fernando Canga, Fernández Díez Servando, Herreros-Rodríguez Jaime, García-Cobos Elvira, Álvarez-Santullano Marina Mata, López-Manzanares Lydia, Mosqueira Antonio J, Vela Desojo Lydia, López-Lozano Juan José, López-Valdés Eva, Sánchez-Sánchez Rafael, Molina-Arjona José Antonio

机构信息

Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain; Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

出版信息

Mov Disord. 2015 Apr;30(4):517-24. doi: 10.1002/mds.25988. Epub 2014 Aug 11.

Abstract

α-Synuclein inclusions have been identified in the brain and some parts of the enteric nervous system in Parkinson's disease cases. We aimed to assess these inclusions in gastric mucosa samples from patients with symptomatic Parkinson's disease. Random biopsies were performed by gastroscopy in 28 patients with Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was performed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were the main indications). The clinical definition of cases and controls was made a priori. Six controls had data suggestive of "mild presymptomatic parkinsonism". Biopsy specimens were immunostained for α-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline characteristics of the groups. Positive fibers for the α-synuclein protein were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls (4.3%), and 1 of 6 (16.7%) cases of incident "mild presymptomatic parkinsonism." Neuropathological diagnosis based on α-synuclein immunostaining showed a sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95% (95% CI 76.2-99.9) and area under the receiver operating characteristics curve (AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of α-synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evidence of the underlying neurodegenerative peripheral involvement linked to Parkinson's disease. Further studies are warranted to determine its pathophysiological implications.

摘要

在帕金森病患者的大脑和肠神经系统的某些部位已发现α-突触核蛋白包涵体。我们旨在评估有症状帕金森病患者胃黏膜样本中的这些包涵体。对28例帕金森病患者和29例年龄及性别匹配的对照者进行了胃镜随机活检。对患者进行胃镜检查是为了开始肠内左旋多巴(L-多巴)治疗,对对照者则是出于诊断目的(胃食管反流、贫血和腹痛是主要指征)。病例和对照的临床定义是预先确定的。6名对照者的数据提示“轻度症状前帕金森综合征”。活检标本进行了α-突触核蛋白免疫染色。神经病理学诊断是事后确定的。两组的基线特征没有差异。在28例帕金森病患者中的17例(60.7%)、23例对照者中的1例(4.3%)以及6例“轻度症状前帕金森综合征”新发病例中的1例(16.7%)观察到α-突触核蛋白阳性纤维。基于α-突触核蛋白免疫染色的神经病理学诊断显示敏感性为85%(95%置信区间[CI]62.1 - 96.8),特异性为95%(95%CI 76.2 - 99.9),受试者操作特征曲线下面积(AUC)为0.90(95%CI 0.80 - 1.00)。未发生不良事件。检测胃黏膜中的α-突触核蛋白包涵体是一种有用且安全的工具,可提供与帕金森病相关的潜在神经退行性周围受累的体内证据。有必要进行进一步研究以确定其病理生理学意义。

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