Abstracts and Commentary
Synopsis: These data prove the high diagnostic value of our objective EEG criteria in CJD.
Source: Steinhoff BJ, et al. Diagnostic Value of Periodic Complexes in Creutzfeldt-Jakob Disease. Ann Neurol. 2004; 56:702-708.
Sporadic Creutzfeldt-Jakob Disease (SCJD) is the most frequent human prion disease, and always has a fatal course. The diagnosis is proved only by brain biopsy or post-mortem examination. Non-invasive diagnostic methods such as the presence in CSF of the 14-3-3 protein,1 or MRI appearance2 have been proposed, but lack sufficient sensitivity to replace tissue diagnosis.
In 1996, Steinhoff et al3 published electroencephalogram (EEG) criteria to define periodic sharp-wave complexes (PSWCs) diagnostic of CJD (see Table).
Diagnostic Criteria For PSWCs in sCJD
In the present study, Steinhoff and colleagues investigated sensitivity, specificity, and predictive values of these EEG criteria in cases of autopsy that confirmed (n = 150) or excluded (n = 56) CJD.
Clinical symptoms alone were sufficient for the correct diagnosis of CJD in 139 patients (93%). In the non-CJD patients, clinical criteria suggested a false diagnosis of CJD in 34 of 56 (61%). Therefore, clinical criteria alone achieved a sensitivity of 93% and a specificity of 39%. The positive predictive value (PPV) was 80% (139/173), and the negative predictive value (NPV) was 67% (22/33).
In CJD patients, typical EEG findings were apparent in 96 (64%). The first typical EEG was recorded 3.7 ± 3.1 months after the onset of disease. In 54 CJD patients (36%), typical EEG criteria were not satisfied.
In the non-CJD group, an EEG typical for sCJD was found in 5 patients (9%). At autopsy, 4 of them had Alzheimer’s disease, and 1 had multiple cerebral infarcts. Therefore, the EEG criteria for CJD used alone had a sensitivity of 64% and a specificity of 91%. The PPV was 95% (966/101) and the NPV was 49% (51/105).
Of the 150 autopsy-proven cases of CJD, 94 had been classified as probable, based on both clinical findings and EEG results. The diagnostic sensitivity of the clinical and EEG criteria when combined was 63%. Only 1 non-CJD patient fulfilled both criteria and was misclassified as probable CJD. Therefore, when both criteria were applied, the specificity was 98%, PPV and NPV were 99% and 49%, respectively.
In CJD, PSWCs are a specific diagnostic indicator, and are able to differentiate the sporadic form of CJD from other prion diseases. PSWCs have been recorded only occasionally in familial CJD, but have not been reported to occur in cases of Kuru, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, or new variant CJD.
In this study the combined specificity of the established clinical and EEG criteria was 97%. Clinicians, especially neurosurgeons and pathologists who must handle infectious tissues, can look forward with hope to the time when clinical and EEG criteria, combined with MRI and other studies, will yield a definitive ante mortem diagnosis of sCJD, without the need for brain biopsy. — John J. Caronna
Dr. Caronna, Vice-Chairman, Department of Neurology, Cornell University Medical Center; Professor of Clinical Neurology, New York Hospital, is Associate Editor of Neurology Alert.
1. World Health Organization Consensus on Criteria for Diagnosis of Sporadic CJD. Wkly Epidemiml Rec. 1998;73:361-365.
2. Schroter A, et al. Arch Neurol. 2000;57;1751-1757.
3. Steinhoff BJ, et al. Arch Neurol. 1996;53:162-166.