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Creutzfeldt-Jakob disease

Orpha number ORPHA204
Synonym(s) -
Prevalence 1-9 / 1 000 000
Inheritance Autosomal dominant
Not applicable
Age of onset Adult
ICD-10
  • A81.0
ICD-O -
OMIM
UMLS
  • C0022336
MeSH
  • D007562
MedDRA
  • 10011384
SNOMED CT
  • 792004

Summary

Creutzfeldt-Jakob's disease (CJD) is the most common form of human transmissible spongiform encephalopathy (TSE). The prevalence is 0.6 - 1.5 / 1,000,000. About 85% of cases are sporadic, 10% are genetic, while 5% are iatrogenic. Incubation periods are long and totally silent, and the disorder is always fatal. CJD causes degeneration of the nervous system without eliciting immune or inflammatory reaction, and is associated with accumulated amounts of an abnormal isoform of the prion protein (PrP). Sporadic CJD occurs around the age of 60 and is fatal within an average of 6 months. It is marked by dementia and neurological signs (myoclonus, cerebellar, visual, pyramidal and extra-pyramidal signs, akinetic mutism). The causes of sporadic CJD are unknown. No mutations have been observed in the PrP gene but homozygous genotype (methionine/methionine or valine/valine) at codon 129 are more frequent than in the general population and represent a risk factor. Inherited CJDs are due to various mutations within the PrP gene. The most frequently encountered mutation in France is the codon 200 mutation, which causes symptoms that are close to those of the sporadic form. The usual investigations are normal, except for the EEG that may show specific periodic modifications and for the MRI that reveal in 50% of cases enhanced signal intensity of caudate nuclei and putania or in the cerebral or cerebellar cortex. The detection of the 14-3-3 protein in the cerebrospinal fluid has a good diagnostic value. Typical neuropathological lesions in the brain (spongiosis, neuronal loss, gliosis) or the presence of the abnormal prion protein lead to a definite diagnosis. Clinical features of iatrogenic CJDs after dura mater grafts resemble also those of the sporadic CJD, whereas the clinical aspect of CJD after injection of human growth hormone is different: cerebellar ataxia is the first symptom, dementia occurs later, the EEG is rarely characteristic, and progression is slower (18 months on average). The variant form of CJD (vCJD) is the only form of CJD linked to bovine spongiform encephalopathy (BSE) or 'mad cow disease''. The first vCJD cases appeared in the United-Kingdom, where the disease is by far the most frequent. In contrast to the sporadic form, vCJD affects younger persons (median age: 30 years), with a mean duration of 15 months. The onset features include psychiatric symptoms often associated with pain or more or less diffuse dysesthesia. Later on, appear a cerebellar syndrome and pyramidal signs. Dementia occurs late in the disease course and myoclonus is mild. EEG patterns are never periodic and the protein 14-3-3 is only detected in 50% of cases. To date, all affected patients have a homozygous genotype methionine/methionine at codon 129. The diagnosis is suspected by MRI enhanced signals of the thalamic pulvinar nuclei and by the detection of abnormal PrP in tonsil biopsy samples. Definite diagnosis is based on the evidence of neuropathological abnormalities specific to CJD, especially the presence of plaques surrounded by vacuoles and spongiform changes ('florid plaques'') in cerebral biopsies. To date, there is no treatment of the underlying pathological mechanisms of the disease.

Expert reviewer(s)

  • Dr Jean-Philippe BRANDEL

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Detailed information

Clinical practice guidelines
  • DE (2012)
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