Rapidly progressive dementia caused by a prion (proteinaceous infectious agent), described in 1982 by neurologist Stanley Prusiner
One case per million worldwide.
More common in certain parts of the world due to familial cases, e.g. Israel and North Africa.
Caused by a transmissable proteinaceous particle which is a modified version of a normal human protein. It does not contain any nucleic acid. It is resistant to many of the normal methods of sterilisation including heat.
· Sporadic CJD remains the most common type.
· Iatrogenic CJD (iCJD) results from transplantation of tissue from an infected individual, such as corneal grafts, cadaveric pituitary hormones and contaminated neurosurgical instruments. No cases have been shown from blood transfusion products.
· Variant CJD (vCJD) –1996 saw the identification of a ‘new’ form of CJD primarily affecting younger people. There is reasonable evidence that this may be due to the ingestion of Bovine Spongiform Encephalopathy (BSE) infected beef. There have been reported cases of person-to-person transmission by blood transfusion.
Prion diseases appear to have a long incubation period, but once clinically apparent, show rapid progression. Neither the transmission nor the mechanism of action of the prion in CJD is clearly understood. There are other prion diseases such as
· Kuru – which used to be prevalent in Papua New Guinea and is believed to have been spread by ritual cannibalism.
· Scrapie in sheep and BSE in cattle.
· Hereditary prion diseases due to mutations in the gene (PRNP) on chromosome 20 can cause several clinical entities within the same kindred including CJD, Gerstmann–Straussler–Sheinker syndrome and fatal familial insomnia.
It is currently thought that a normal glycoprotein in the brain (the function of which is unknown) undergoes conformational change to become prion protein (PrP). This abnormally conformed protein is resistant to digestion by proteases and tends to form polymers. The disease appears to be propagated further by the abnormally conformed protein inducing normal protein to conformationally change, leading to further polymer formation. In familial cases, it appears that the abnormal protein arises spontaneously due to a mutation of the gene encoding PrP, whereas in other cases there appears to be inoculation or ingestion of the prion, which is transported to the nervous system and can then cause prion disease in susceptible individuals.
CJD presents as a rapid onset of dementia, characteristically with myoclonic jerks (in ∼90% of patients, but not in vCJD). Extrapyramidal signs and upper motor neurone signs occur frequently. Sensory signs and symptoms and psychiatric symptoms occur in vCJD, but are uncommon in other forms.
Neuronal loss, increase in glial cells, lack of inflammation and small vacuoles in the neuropil which has lead to the term ‘spongiform encephalopathy’.
CT brain scans are usually normal, but serial scans may show rapidly progressive ventricular enlargement and cortical atrophy. MRI in vCJD only shows increased T2 signal in the basal ganglia.
EEG is often abnormal in sporadic CJD.
CSF is unremarkable and has normal protein levels. There are raised levels of a normal intraneuronal protein (14-3-3 protein) detectable in the CSF of patients with CJD, which may simply imply rapid neuronal death, but can be a useful marker.
There is no reliable method of confirming diagnosis except by brain biopsy or postmortem. vCJD may be suggested by the finding of prion protein on tonsillar biopsy, although this is not yet a reliable clinical test.
The disease is fatal within 1 year of onset of symptoms for most forms, but 2 years in vCJD.