Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021.
Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021.
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DOI：
10.1001/jamanetworkopen.2022.25098
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发表时间：
2022-08-01
影响因子：
13.8
通讯作者：
Day, Gregory S.
中科院分区：
文献类型：
--
作者：
Shir, Dror;Lazar, Evelyn B.;Graff-Radford, Jonathan;Aksamit, Allen J.;Cutsforth-Gregory, Jeremy K.;Jones, David T.;Botha, Hugo;Ramanan, Vijay K.;Prusinski, Christian;Porter, Amanda;Day, Gregory S.
在现代评估的患者中，与历史上与克雅氏病(CJD)相关的临床特征和测试相关的诊断效用是什么？在这项包括115例患者的队列研究中，脑脊液实时抖动诱发转换分析、总tau和定型信号异常在磁共振成像上的诊断性能较高，而在脑电图上对肌阵挛和周期性放电的诊断效率较低。肌阵挛的存在、视觉或小脑表现以及脑脊液中14-3-3蛋白和总tau水平的升高与死亡时间的缩短独立相关。这些发现可能会指导对疑似CJD患者的可及性测试的优先顺序和解释。这项队列研究评估了潜在的克雅氏病患者的临床特征和诊断测试，以及这些特征与预后的关系。利用实时抖动诱导转换(RT-QuIC)方法检测脑脊液(CSF)中的普恩蛋白，改变了散发性克雅氏病(CJD)的诊断方法，有助于更早和更全面地识别受影响的患者。目前尚不清楚扩大对受影响患者的认识可能如何影响与CJD相关的临床特征和诊断试验的诊断和预后相关性。评估CJD患者的临床特征和诊断试验，并确定这些特征与预后的关系。这项队列研究纳入了明尼苏达州罗切斯特、佛罗里达州杰克逊维尔和亚利桑那州斯科茨代尔的梅奥诊所企业三级护理中心治疗的CJD患者的电子医疗记录中的数据。参与者包括2014至2021年评估的确诊或可能患有CJD的患者。分析了2021年10月至2022年1月的数据。与CJD相关的主要表现、临床特征和诊断试验。令人感兴趣的结果是临床特征和可获得的诊断测试对可能的CJD的敏感性和预后价值。总共确定了115名患者，其中40名(35%)确诊为CJD。平均发病年龄(SD)为64.8(9.4)岁，其中女性68例(59%)。临床标志物(肌阵挛)和历史上被认为是CJD患者的检测的敏感性很差(例如，定型的脑电异常：105名患者中有17名(16%)；脑脊液蛋白14-3-3水平升高：90名患者中有54名[60%])。相比之下，诊断敏感性较好的生物标志物包括RT-QuIC(71例患者中66例(93%))，脑脊液总tau(T-tau)水平>1149 pg/mL(92例患者中81例(88%))，以及磁共振成像特征信号异常(115例患者中88例(77%))。多变量线性回归证实，肌阵挛患者生存期较短(差异，−125.9[95%CI，−236.3至−15.5]天；P = .03)，视觉或小脑体征(差异，−180.2[95%CI，−282.2至−78.2d；P <； .001)，脑脊液蛋白14-3-3水平升高(差异，−193[95%CI，−304.9至−82.9]天；P <； .001)和T-tau水平升高(每升高1000pg/ml，−9.1d[95%CI，−17.7to−1.0]天；P = 0.04)。这些结果表明，脑脊液RT-QuIC、脑脊液T-tau水平升高和定型磁共振成像异常与CJD的诊断有关，而其他临床表现(如肌阵挛)、定型脑电异常和脑脊液蛋白14-3-3水平的诊断价值较低。视觉或小脑特征、肌阵挛、脑脊液14-3-3和T-tau水平可能与病程有关，因此有理由继续将其纳入CJD患者的评估。
What is the diagnostic utility associated with clinical features and tests historically associated with Creutzfeldt-Jakob disease (CJD) in patients evaluated in the modern era? In this cohort study including 115 patients, the diagnostic performance of cerebrospinal fluid real-time quaking-induced conversion assays, total tau, and stereotyped signal anomalies on magnetic resonance imaging was high, while the diagnostic yield of myoclonus and periodic discharges on electroencephalography was low. The presence of myoclonus, visual or cerebellar findings, and elevated levels of protein 14-3-3 and total tau in cerebrospinal fluid were independently associated with shorter time to death. These findings may guide prioritization and interpretation of accessible tests in patients with suspected CJD. This cohort study evaluates clinical features and diagnostic testing in patients presenting with potential Creutzfeldt-Jakob disease and the associations of these features with prognosis. Detection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD. To evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis. This cohort study incorporated data from electronic medical records of patients with CJD treated at Mayo Clinic Enterprise tertiary care centers in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona. Participants included patients with definite or probable CJD assessed from 2014 to 2021. Data were analyzed October 2021 to January 2022. Dominant presentation, clinical features, and diagnostic tests associated with CJD. The outcomes of interest were the sensitivity and prognostic value of clinical features and accessible diagnostic tests at presentation with possible CJD. A total of 115 patients were identified, including 40 patients (35%) with definite CJD. Mean (SD) age at symptom onset was 64.8 (9.4) years, and 68 patients were women (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (eg, stereotyped electroencephalography anomalies: 17 of 105 patients [16%]; elevated CSF protein 14-3-3 levels: 54 of 90 patients [60%]). By comparison, biomarkers with good diagnostic sensitivity at presentation included RT-QuIC (66 of 71 patients [93%]), CSF total tau (T-tau) level greater than 1149 pg/mL (81 of 92 patients [88%]), and characteristic signal anomalies on magnetic resonance imaging (88 of 115 patients [77%]). Multivariable linear regression confirmed shorter survival in patients with myoclonus (difference, −125.9 [95% CI, −236.3 to −15.5] days; P = .03), visual or cerebellar signs (difference, −180.2 [95% CI, −282.2 to −78.2] days; P < .001), elevated CSF protein 14-3-3 levels (difference, −193 [95% CI, −304.9 to −82.9] days; P < .001), and elevated T-tau level (difference for every 1000 pg/mL elevation, −9.1 [95% CI, −17.7 to −1.0] days; P = .04). These findings suggest that CSF RT-QuIC, elevated CSF T-tau level, and stereotyped magnetic resonance imaging anomalies were associated with the diagnosis of CJD, while other clinical findings (eg, myoclonus), stereotyped electroencephalography anomalies, and CSF protein 14-3-3 levels offered less diagnostic value. Visual or cerebellar features, myoclonus, and CSF 14-3-3 and T-tau levels may be associated with disease duration, justifying continued inclusion in the evaluation of patients suspected to have CJD.
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