Mastrangelo Andrea, Mammana Angela, Baiardi Simone, Tiple Dorina, Colaizzo Elisa, Rossi Marcello, Vaianella Luana, Polischi Barbara, Equestre Michele, Poleggi Anna, Capellari Sabina, Ladogana Anna, Parchi Piero
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy.
J Neurol Neurosurg Psychiatry. 2023 Feb;94(2):121-129. doi: 10.1136/jnnp-2022-330153. Epub 2022 Nov 25.
The introduction of the prion Real-Time Quaking-Induced Conversion assay (RT-QuIC) has led to a revision of the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD).Validation studies are needed for the amended criteria, especially for their diagnostic value in the clinical setting.
We studied 1250 patients with suspected CJD referred for diagnosis to two Italian reference centres between 2010 and 2020. Focusing on the first diagnostic assessment, we compared the diagnostic value of the old and the amended criteria and that of different combinations of clinical variables and biomarker results.
The studied cohort comprised 850 participants with CJD (297 definite sCJD, 151 genetic CJD, 402 probable sCJD) and 400 with non-CJD (61 with neuropathology). At first clinical evaluation, the sensitivity of the old criteria (76.8%) was significantly lower than that of the amended criteria (97.8%) in the definite CJD cohort with no difference between definite and probable sCJD cases. Specificity was ~94% for both criteria against the non-CJD cohort (82.0% against definite non-CJD group). Cerebrospinal fluid (CSF) RT-QuIC was highly sensitive (93.9%) and fully specific against definite non-CJD patients. Limiting the criteria to a positive RT-QuIC or/and the combination of a clinical course compatible with possible CJD with a positive MRI (Q-CM criteria) provided higher diagnostic accuracy than both the old and amended criteria, overcoming the suboptimal specificity of ancillary test results (ie, CSF protein 14-3-3).
CSF RT-QuIC is highly sensitive and specific for diagnosing CJD in vitam. The Q-CM criteria provide a high diagnostic value for CJD.
朊病毒实时震颤诱导转化检测法（RT-QuIC）的引入促使散发性克雅氏病（sCJD）的诊断标准得到修订。修订后的标准需要进行验证研究，尤其是在临床环境中的诊断价值。
我们研究了2010年至2020年间转诊至两个意大利参考中心进行诊断的1250例疑似克雅氏病患者。聚焦于首次诊断评估，我们比较了旧标准和修订后标准的诊断价值，以及临床变量和生物标志物结果的不同组合的诊断价值。
研究队列包括850例克雅氏病患者（297例确诊sCJD，151例遗传性克雅氏病，402例可能sCJD）和400例非克雅氏病患者（61例有神经病理学检查结果）。在首次临床评估时，在确诊克雅氏病队列中，旧标准的敏感性（76.8%）显著低于修订后标准的敏感性（97.8%），确诊和可能sCJD病例之间无差异。两种标准针对非克雅氏病队列的特异性均约为94%（针对确诊非克雅氏病组为82.0%）。脑脊液（CSF）RT-QuIC对确诊非克雅氏病患者具有高度敏感性（93.9%）且完全特异。将标准限制为RT-QuIC阳性或/和临床病程符合可能克雅氏病且MRI阳性的组合（Q-CM标准）比旧标准和修订后标准具有更高的诊断准确性，克服了辅助检测结果（即脑脊液蛋白14-3-3）特异性欠佳的问题。
脑脊液RT-QuIC在生前诊断克雅氏病方面具有高度敏感性和特异性。Q-CM标准对克雅氏病具有较高的诊断价值。
