Zerr I, Bodemer M, Otto M, Poser S, Windl O, Kretzschmar H A, Gefeller O, Weber T
Neurologische Klinik und Poliklinik, Georg-August-Universität, Göttingen, Germany.
Lancet. 1996 Sep 28;348(9031):846-9. doi: 10.1016/S0140-6736(96)08077-4.
The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on clinical and electroencephalographic criteria which do not allow a reliable diagnosis to be made during life.
Serum and cerebrospinal fluid (CSF) samples were obtained after informed consent from relatives of suspected cases of CJD referred to the German CJD surveillance unit. CSF samples from 58 definite (neuropathologically verified), 46 probable, and 34 possible CJD cases, and from 44 patients without CJD were analysed by two-dimensional gel electrophoresis (2-DE). Two investigators blinded to clinical findings recorded the presence of two proteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared with the determination of neuron-specific enolase (NSE) in CSF. NSE concentrations of more than 35 ng/mL were considered indicative of CJD.
p130/131 was detected in 81% of definite (47/58), 80% of probable (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases. NSE concentrations of more than 35 ng/mL were seen in 79% of definite (46/58), 80% of probable (37/46), 59% of possible (20/34) CJD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% CI 0.86-0.99). Of 13 cases initially classified as possible and later reclassified as definite, ten cases were identified correctly by the 2-DE analysis, indicating a better diagnostic accuracy of this test compared with the current clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE.
2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG.
克雅氏病（CJD）的诊断基于临床和脑电图标准，这些标准无法在患者生前做出可靠诊断。
在获得德国CJD监测单位转诊的疑似CJD病例亲属的知情同意后，采集血清和脑脊液（CSF）样本。对58例确诊（经神经病理学证实）、46例疑似和34例可能的CJD病例以及44例非CJD患者的CSF样本进行二维凝胶电泳（2-DE）分析。两名对临床结果不知情的研究人员记录两种蛋白质p130/131的存在情况。计算这两名研究人员之间一致性水平的kappa值。将所得结果与CSF中神经元特异性烯醇化酶（NSE）的测定结果进行比较。CSF中NSE浓度超过35 ng/mL被认为提示CJD。
在81%的确诊（47/58）、80%的疑似（37/46）、68%的可能（23/34）CJD病例中检测到p130/131，而在其他44例病例中均未检测到。CSF中NSE浓度超过35 ng/mL在79%的确诊（46/58）、80%的疑似（37/46）、59%的可能（20/34）CJD病例以及9%的其他病例（4/43）中出现。CSF的2-DE检测的阳性预测值为100%，阴性预测值为69%。在141张2-DE凝胶的子集中，两名评估人员检测p130/131的一致性水平kappa值为0.93（95%CI 0.86-0.99）。在最初分类为可能但后来重新分类为确诊的13例病例中，2-DE分析正确识别出10例，表明该检测的诊断准确性优于当前的临床分类。经神经病理学分类为其他的9例病例中，2-DE均未检测到p130/131。
p130/131的2-DE检测是诊断CJD的特异性检测。这些数据表明，除了目前公认的病程少于2年的快速进展性痴呆、典型神经体征和脑电图周期性锐波复合波等诊断标准外，应将p130/131的检测纳入疑似CJD的诊断标准。
