Creutzfeldt–Jakob Disease - Diagnosis

Diagnosis

The diagnosis of CJD is suspected when there are typical clinical symptoms and signs such as rapidly progressing dementia with myoclonus. Further investigation can then be performed to support the diagnosis including

• Electroencephalography — often has characteristic triphasic spikes
• Cerebrospinal fluid analysis for 14-3-3 protein
• MRI of the brain — often shows high signal intensity in the caudate nucleus and putamen bilaterally on T2-weighted images.
• Research in 2010 and 2011 identified a possible blood test for CJD. The test attempts to identify the prion responsible for the disease. However, it was unable to detect the prions in those in early stages of the disease.

Diffusion Weighted Imaging (DWI) images are the most sensitive. In about 24% of cases DWI shows only cortical hyperintensity; in 68%, cortical and subcortical abnormalities; and in 5%, only subcortical anomalies. The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD.

Clinical testing for CJD has always been an issue. Diagnosis has mostly been based on clinical and physical examination of symptoms. In recent years, studies have shown that the tumour marker Neuron-specific enolase (NSE) is often elevated in CJD cases, however its diagnostic utility is primarily seen when combined with a test for the 14-3-3 protein. As of 2010, screening tests to identify infected asymptomatic individuals, such as blood donors, are not yet available, though methods have been proposed and evaluated.

In 2010, a team from New York described detection of PrPSc even when initially present at only one part in one hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA) and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of great value in surveillance as a blood or urine-based screening test for CJD.

In one third of patients with sporadic CJD, deposits of "prion protein (scrapie)," PrPSc, can be found in the skeletal muscle and/or the spleen. Diagnosis of vCJD can be supported by biopsy of the tonsils, which harbour significant amounts of PrPSc; however, biopsy of brain tissue is the definitive diagnostic test. Due to its invasiveness, biopsy will not be done if clinical suspicion is sufficiently high or low. A negative biopsy does not rule out CJD, since it may predominate in a specific part of the brain

The classic histologic appearance is spongiform change in the gray matter: the presence of many round vacuoles from one to 50 micrometres in the neuropil, in all six cortical layers in the cerebral cortex or with diffuse involvement of the cerebellar molecular layer. These vacuoles appear glassy or eosinophilic and may coalesce. Neuronal loss and gliosis are also seen. Plaques of amyloid-like material can be seen in the neocortex in new-variant CJD.

Unfortunately, vacuolization can be seen in other disease states. Diffuse cortical vacuolization occurs in Alzheimer's, and superficial cortical vacuolization occurs in ischemia and frontotemporal dementia. These vacuoles appear clear and punched-out. Larger vacuoles encircling neurons, vessels, and glia are a possible processing artifact.

• Clinical and Pathologic Characteristics:

• An abnormal signal in the posterior thalamus on T2- and diffusion-weighted images and fluid-attenuated inversion recovery sequences on brain magnetic resonance imaging (MRI); in the appropriate clinical context, this signal is highly specific for vCJD. (Source: CDC)