Although a possible or probable diagnosis can be made during the clinical illness, the only way to definitely confirm CJD is by brain biopsy (not recommended due to transmission risks) or a brain only autopsy. This gives families an accurate diagnosis, or in some cases, establishes an alternative diagnosis that can be important for the family to develop closure over their loved one’s illness. This also can confirm if the patient died of CJD or variant CJD. The brains of patients with either sCJD or vCJD contain abnormal forms of prion protein. This abnormal form of the protein is linked directly to TSEs and constitutes an excellent marker for this group of diseases. The examination of the vCJD brain shows widespread deposits of abnormal prion protein, called florid plaques. This form of plaque is not seen in sCJD. Variant CJD can also be detected in lymphatic tissue (spleen, tonsils and lymph nodes), unlike sCJD.
A DNA test is however required to establish whether a CJD case confirmed by a neuropathologic examination of the brain is sporadic or genetic.
The main indications leading to a possible diagnosis of CJD are rapid dementia and two or more of a range of neurological symptoms including unsteady gait or coordination, visual impairment, weakness or abnormal movements, sudden jerking movements and akinetic mutism. The brains of people and animals affected with a prion disease have a “spongy” appearance microscopically caused by numerous tiny holes (vacuoles). This characteristic damage is known as spongiform encephalopathy. When the diagnosis of CJD is suspected, a number of investigations are usually carried out. These are helpful in excluding other conditions and some findings can support a diagnosis of probable CJD.
An electroencephalogram (EEG) often shows a characteristic change in the brain waves in sporadic CJD. In about 60% of sporadic CJD patients there will be a characteristic abnormality of brain wave pattern.
Magnetic resonance imaging (MRI) produces an image of the brain which is useful in ruling out other conditions such as a brain tumour as well as supporting the diagnosis of CJD. It is used to look at brain structure and there are features on the MRI that are very characteristic of CJD. Sometimes, a brain MRI can be helpful in differentiating CJD from vCJD prior to a definitive diagnosis at autopsy.
A particular protein called 14-3-3 in the cerebrospinal fluid (CSF), associated with the rapid loss of brain cells, is very helpful in the diagnosis of sporadic CJD, and although not perfect, it has a sensitivity of 85–90%. CSF testing looks for the presence of the 14-3-3 protein which has nothing to do with the prion protein. This non-specific 14-3-3 protein is believed to be present in the spinal fluid when affected neurons die and release this normal cellular protein that leaks into the spinal fluid. For further information contact the Australian National CJD Registry (ANCJDR).
The ANCJDR is continually looking to adopt improvements in diagnostic capacity, including such techniques as the RT-QuIC.