Abstract & Commentary
Source: Geschwind, et al. Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease. Arch Neurol. 2003;60:813-816.
The value of the 14-3-3 test for establishing a diagnosis of probable sporadic Creutzfeldt-Jakob disease (CJD) has been suggested to be as high as 96-100% in several reports. This has been established by reports from the World Health Organization, which revised its diagnostic criteria for probable sporadic CJD to allow substitution of a positive 14-3-3 test for a positive electroencephalogram, provided the disease has less than 2 years’ duration. A number of other studies, however, has suggested that the test lacks both sensitivity and specificity. In the present report, 32 patients who had definite CJD established by biopsy or autopsy confirmation were studied for 14-3-3 reactivity. Seventeen of the 32 patients had a positive result. This yields a sensitivity of only 53%. Geschwind and colleagues concluded that the test was only moderately sensitive in establishing the diagnosis.
Commentary
The present paper is consistent with that of a number of other studies, which suggest that the 14-3-3 test, although useful, is frequently insensitive in establishing a diagnosis of CJD. Another study showed a sensitivity of 61%, yet a relatively high specificity if one used a cutoff of a value of more than 8 ng/mL. When a lower threshold was used, the sensitivity increased, but the specificity fell dramatically to only approximately 50%. The 14-3-3 protein is a marker for chronic neuronal damage. It can be increased by a variety of other illnesses such as rapidly progressive Alzheimer’s disease, rapidly progressive frontotemporal dementia, Hashimoto’s encephalitis, vasculitis, or diffuse intravascular lymphomatosis. The 14-3-3 protein is also increased in patients with multiple sclerosis with myelitis.1 In our experience, we have had a number of biopsy-confirmed cases recently in which the test was negative. Findings of enhanced signal in the cortical ribbon on diffusionweighted magnetic resonance imaging and a characteristic EEG may have greater diagnostic use. — M. Flint Beal, MD. Dr. Beal, Department of Neurology; Cornell University Medical College, is Editor of Neurology Alert.
Reference
1. Satoh J, et al. J Neurol Sci. 2003;212:11-20.
The value of the 14-3-3 test for establishing a diagnosis of probable sporadic Creutzfeldt-Jakob disease (CJD) has been suggested to be as high as 96-100% in several reports. In the present report, 32 patients who had definite CJD established by biopsy or autopsy confirmation were studied for 14-3-3 reactivity.
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