Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years
Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years
复制标题
DOI：
10.1093/brain/aws238
复制
发表时间：
2012-10-01
期刊：
影响因子：
14.5
通讯作者：
Zerr, Inga
中科院分区：
文献类型：
--
作者：
Stoeck, Katharina;Sanchez-Juan, Pascual;Zerr, Inga
到目前为止，脑脊液分析，特别是蛋白14 - 3 - 3测试，提出了一个重要的方法，在确定克雅氏病病例。然而，14 - 3 - 3测试的一个特殊批评点是快速痴呆症鉴别诊断的特异性。在过去几年中，不断观察到国家监测中心的脑脊液转诊增加，这引起了人们对特异性下降的关切，因为在各种神经系统疾病中进行的脑脊液检测数量增加。在欧洲共同体支持的纵向多中心研究框架内，我们分析了快速进展性痴呆的诊断谱、它们对14 - 3 - 3特异性的潜在影响以及其他痴呆标志物的结果。（τ，磷酸化tau和淀粉样蛋白-β（1 - 42）），并评估1998 - 2008年14 - 3 - 3在克雅氏病诊断中的特异性。在参与研究的中心，共对29022份脑脊液样本进行了14 - 3 - 3蛋白和其他脑脊液痴呆标志物的分析，这些患者患有快速痴呆和疑似克雅氏病。10731例患者可获得明确诊断。蛋白14 - 3 - 3的特异性进行了分析，克雅氏病方面增加脑脊液测试，每年和频谱的鉴别诊断。进行了环形试验，以确保报告期间各中心之间的可比性。在各中心的观察时间段内，蛋白14 - 3 - 3检测在克雅氏病诊断中的特异性保持较高且稳定（总特异性92%;与仅确诊患者相比：特异性90%）。然而，测试特异性在鉴别诊断方面有所不同。在与其他神经退行性疾病（95 - 97%）和非神经系统疾病（91 - 97%）的鉴别中获得了高的14 - 3 - 3特异性。我们观察到急性神经系统疾病鉴别诊断的特异性较低（82 - 87%）。所有中心每年脑脊液检测转诊的显著和持续增加不影响14 - 3 - 3检测特异性，也未观察到鉴别诊断谱的变化。脑脊液蛋白14 - 3 - 3检测仍是诊断Creutzfeldt-Jakob病的一项重要试验。由于急性神经系统事件的特异性丧失，阳性14 - 3 - 3结果的解释需要在临床背景下进行。快速进展性痴呆的鉴别诊断范围从神经退行性痴呆到急性神经系统疾病（如炎症性疾病和非神经源性疾病）所致痴呆不等。
To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt-Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study ('cerebrospinal fluid markers') we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-beta(1-42)) and evaluated the specificity of 14-3-3 in Creutzfeldt-Jakob disease diagnosis for the years 1998-2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt-Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt-Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt-Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95-97%) and non-neurological conditions (91-97%). We observed lower specificity in the differential diagnoses of acute neurological diseases (82-87%). A marked and constant increase in cerebrospinal fluid test referrals per year in all centres did not influence 14-3-3 test specificity and no change in spectrum of differential diagnosis was observed. Cerebrospinal fluid protein 14-3-3 detection remains an important test in the diagnosis of Creutzfeldt-Jakob disease. Due to a loss in specificity in acute neurological events, the interpretation of positive 14-3-3 results needs to be performed in the clinical context. The spectrum of differential diagnosis of rapid progressive dementia varied from neurodegenerative dementias to dementia due to acute neurological conditions such as inflammatory diseases and non-neurological origin.