A definitive diagnosis of CJD can only be made by examination of brain tissue (biopsy or autopsy). This is the only current method of confirming the diagnosis of both sporadic CJD and variant CJD.
Diagnostic tests that are not confirmatory but are used in conjunction with clinical symptoms to help make a diagnosis of possible or probable CJD include:
Magnetic Resonance Imaging (MRI)
MRI is the most useful diagnostic test for CJD. The recommended imaging is T2 and proton density axial images with 3 mm slice thickness, FLAIR axial and sagittal images at 3 mm slice thickness, T1 images, and diffusion-weighted images (DWI).
MRIs can have findings of likely CJD and are useful in ruling out other neurological diseases. vCJD and sCJD have different finds on MRI.
Distinctive abnormalities may be seen in patients with CJD but are not definitive. As the disease progresses, EEG findings also change. In the early stages of sCJD, the EEG may be normal or may show non-specific slowing. With progression, biphasic or triphasic periodic complexes that evolve into periodic sharp wave complexes appear. In vCJD cases, EEG findings are usually absent or they may be defined as nonspecific, slow wave abnormalities.
Cerebral Spinal Fluid (CSF)
14-3-3 protein – elevated levels of the 14-3-3 protein in CSF may be seen in patients with CJD. The 14-3-3 immunoassay is not a screening test but may be helpful in clinically diagnosing patients exhibiting rapidly progressive dementia and is used when a diagnosis of CJD is suspected.
A positive test may also be seen in a number of other neurological diseases, and is not considered a confirmatory test for CJD. Other conditions such as a recent stroke, neoplasm, or encephalitis can cause a positive CSF test. A negative 14-3-3 CSF test cannot exclude the diagnosis of CJD while a positive test could reflect another disease.
Tau protein – A positive CSF tau test can be helpful in diagnosing CJD. The National Prion Disease Pathology Surveillance Center (NPDPSC) performs tha tau protein test along with the 14-3-3 protein test. A positive CSF test for tau protein is not a definitive diagnostic test for CJD and must be interpreted in the context of clinical disease and pathological examination of brain tissue. Elevations in tau protein may also be found in other neurological diseases.
Confirmatory diagnosis of CJD requires pathologic examination of brain tissue.
Brain biopsy – may detect CJD but should not be used to rule it out. False negatives can occur because samples collected may not include the brain tissue where the abnormal prions are present.
Brain autopsy – is the only definitive test to diagnose CJD.
In the United States, the National Prion Disease Pathology Surveillance Center (NPDPSC) provides free autopsy services. This national reference laboratory, established by the Centers for Disease Control and sponsored by the American Association of Neuropathologists, provides CJD diagnostic testing.
The California Department of Public Health encourages providers to speak with family members of patients with suspected CJD to consider a brain autopsy. Our continued efforts to conduct surveillance and learn about CJD will be greatly enhanced by increasing the proportion of CJD cases that are confirmed through autopsy.
Arrangements for autopsy and laboratory testing can be made through the National Prion Disease Pathology Surveillance Center. Details regarding the collection and shipment of clinical specimens, as well as additional resources available at the National Prion Center, can be obtained from its website (http://www.cjdsurveillance.com) or call (216) 368-0587.