Department of Neurology, Mayo Clinic, Rochester, Minnesota.
Department of Neurology, Mayo Clinic, Jacksonville, Florida.
JAMA Netw Open. 2022 Aug 1;5(8):e2225098. doi: 10.1001/jamanetworkopen.2022.25098.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
使用实时震颤诱导转化（RT-QuIC）检测脑脊液（CSF）中的朊病毒蛋白改变了散发性克雅氏病（CJD）的诊断方法，使受影响患者的早期和更完整的识别成为可能。目前尚不清楚对受影响患者的认识扩大如何影响与 CJD 相关的临床特征和诊断测试的诊断和预后相关性。
评估出现 CJD 的患者的临床特征和诊断测试，并确定这些特征与预后的相关性。
设计、地点和参与者：这项队列研究纳入了明尼苏达州罗切斯特市梅奥诊所企业三级护理中心、佛罗里达州杰克逊维尔和亚利桑那州斯科茨代尔治疗的 CJD 患者的电子病历数据。参与者包括 2014 年至 2021 年评估的明确或可能的 CJD 患者。数据分析于 2021 年 10 月至 2022 年 1 月进行。
与 CJD 相关的显性表现、临床特征和诊断测试。
感兴趣的结果是可能的 CJD 患者就诊时临床特征和可及诊断测试的敏感性和预后价值。
共确定了 115 名患者，其中 40 名（35%）患者患有明确的 CJD。症状发作时的平均（SD）年龄为 64.8（9.4）岁，68 名患者为女性（59%）。历史上认为疑似 CJD 患者的临床标志物（肌阵挛）和测试的敏感性较差（例如，刻板脑电图异常：105 名患者中的 17 例[16%]；升高的 CSF 蛋白 14-3-3 水平：90 名患者中的 54 例[60%]）。相比之下，在就诊时具有良好诊断敏感性的生物标志物包括 RT-QuIC（71 名患者中的 66 例[93%]）、CSF 总 tau（T-tau）水平大于 1149 pg/mL（92 名患者中的 81 例[88%]）和磁共振成像上的特征信号异常（115 名患者中的 88 例[77%]）。多变量线性回归证实肌阵挛患者的生存时间更短（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-78.2]天；P < .001）、升高的 CSF 蛋白 14-3-3 水平（差异，-193[95%CI，-304.9 至-82.9]天；P < .001）和升高的 T-tau 水平（每增加 1000 pg/mL，差异为-9.1[95%CI，-17.7 至-1.0]天；P = .04）。
这些发现表明 CSF RT-QuIC、升高的 CSF T-tau 水平和刻板的磁共振成像异常与 CJD 的诊断相关，而其他临床发现（例如肌阵挛）、刻板的脑电图异常和 CSF 蛋白 14-3-3 水平提供的诊断价值较低。视觉或小脑特征、肌阵挛以及 CSF 14-3-3 和 T-tau 水平可能与疾病持续时间相关，这证明了它们在疑似 CJD 患者评估中的持续纳入是合理的。
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