Grossauer Anna, Hemicker Greta, Krismer Florian, Peball Marina, Djamshidian Atbin, Poewe Werner, Seppi Klaus, Heim Beatrice
Department of Neurology Medical University of Innsbruck Innsbruck Austria.
Mov Disord Clin Pract. 2023 Mar 15;10(5):737-747. doi: 10.1002/mdc3.13710. eCollection 2023 May.
Real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) have been developed to detect minute amounts of amyloidogenic proteins via amplification techniques and have been used to detect misfolded α-synuclein (αSyn) aggregates in the cerebrospinal fluid (CSF) and other source materials of patients with Parkinson's Disease and other synucleinopathies.
The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of αSyn seed amplification assays (αSyn-SAAs), including RT-QuIC and PMCA, using CSF as source material to differentiate synucleinopathies from controls.
The electronic MEDLINE database PubMed was searched for relevant articles published until June 30, 2022. Study quality assessment was performed using the QUADAS-2 toolbox. A random effects bivariate model was exploited for data synthesis.
Our systematic review identified 27 eligible studies according to the predefined inclusion criteria, of which 22 were included in the final analysis. Overall, 1855 patients with synucleinopathies and 1378 non-synucleinopathies as control subjects were included in the meta-analysis. The pooled sensitivity and specificity to differentiate synucleinopathies from controls with αSyn-SAA were 0.88 (95% CI, 0.82-0.93) and 0.95 (95% CI, 0.92-0.97), respectively. Evaluating the diagnostic performance of RT-QuIC in a subgroup analysis for the detection of patients with multiple system atrophy the pooled sensitivity decreased to 0.30 (95% CI, 0.11-0.59).
While our study clearly demonstrated a high diagnostic performance of RT-QuIC and PMCA for differentiating synucleinopathies with Lewy bodies from controls, results for the diagnosis of multiple system atrophy were less robust.
实时颤抖诱导转化（RT-QuIC）和蛋白质错误折叠循环扩增（PMCA）已被开发出来，通过扩增技术检测微量淀粉样蛋白生成蛋白，并已用于检测帕金森病和其他突触核蛋白病患者脑脊液（CSF）及其他来源材料中错误折叠的α-突触核蛋白（αSyn）聚集体。
本系统评价和荟萃分析的目的是评估以脑脊液为源材料，使用αSyn种子扩增检测法（αSyn-SAAs，包括RT-QuIC和PMCA）区分突触核蛋白病与对照的诊断准确性。
检索电子MEDLINE数据库PubMed中截至2022年6月30日发表的相关文章。使用QUADAS-2工具箱进行研究质量评估。采用随机效应双变量模型进行数据合成。
根据预定义的纳入标准，我们的系统评价确定了27项符合条件的研究，其中22项纳入最终分析。荟萃分析共纳入1855例突触核蛋白病患者和1378例非突触核蛋白病患者作为对照。使用αSyn-SAA区分突触核蛋白病与对照的合并敏感性和特异性分别为0.88（95%CI，0.82-0.93）和0.95（95%CI，0.92-0.97）。在检测多系统萎缩患者的亚组分析中评估RT-QuIC的诊断性能时，合并敏感性降至0.30（95%CI，0.11-0.59）。
虽然我们的研究清楚地表明RT-QuIC和PMCA在区分路易体突触核蛋白病与对照方面具有较高的诊断性能，但在多系统萎缩诊断方面的结果不太可靠。
