Revision 41 for 'Creutzfeldt-Jakob disease'

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Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that results in a rapidly progressive dementia and other non-specific neurological features and death usually within a year or less from onset.  

On imaging it classically manifests as T2/FLAIR hyperintensities within the basal ganglia, the thalamus, and cortex which also show diffusion restriction on DWI/ADC sequences. 

Epidemiology

Four types of Creutzfeldt-Jakob disease have been described 2,6:

  • sporadic (sCJD): accounts for 85-90% of cases
  • variant (vCJD): mad cow disease, Kuru 
  • familial (fCJD): 10% of cases (these individuals carry a PRPc mutation)
  • iatrogenic

Clinical presentation

Creutzfeldt-Jakob disease is characterized by rapidly progressive dementia, cerebral atrophy, myoclonus and death. Patients with vCJD present mostly with sensory and psychiatric symptoms; patients with sCJD usually present with progressive cognitive impairment and cerebellar symptoms.

Diagnostic markers
  • characteristic results on electroencephalography (EEG)
  • S100
  • 14-3-3 protein: for patients with suspected CJD, CSF 14-3-3 assays should be performed. In diagnosing CJD (the sensitivity is 92%, specificity is 80%).
    A negative 14-3-3 assay may be helpful in reducing the suspicion of sCJD, a positive CSF 14-3-3 assay may be found in a potentially treatable case of dementia. These findings need to be correlated with patient's history as CSF 14-3-3 can be false positive in treatable dementing disorders 7-8.

A definitive diagnosis requires a brain biopsy, although in many institutions the difficulty involved in sterilizing equipment renders a biopsy undesirable. 

Pathology

CJD is thought to be mediated via (infectious) prions, a type of protein, which manifest in sheep as the disease scrapie, and in cows as bovine spongiform encephalopathy. Prions are considered infectious in sense that they can alter the structure of neighboring proteins. 

CJD leads to spongiform degeneration of the brain, which is thought to be caused by the conversion of normal prion protein to proteinaceous infectious particles that accumulate in and around neurons and lead to cell death.

Radiographic features

MRI

MRI findings may be bilateral or unilateral and symmetric or asymmetric, and include:

  • T2:  hyperintensity
  • DWI/ADC: persistent restricted diffusion (considered the most sensitive sign)

Review of sequential studies also typically demonstrates rapidly progressive cerebral atrophy.

Nuclear medicine 
  • hypometabolism on 18FDG-PET studies

Treatment and prognosis

There is currently no curative treatment and the disease is invariably fatal with a mean survival of only 7 months for most cases.

Since 2009, CJD is a notifiable disease in Australia and by law is required to be reported to the Department of Health. CJD is also notifiable in the United Kingdom, USA and Canada.

History and etymology

It was named after Hans Gerhard Creutzfeldt, a German neurologist who first described the condition in 1920, and Alfons Maria Jakob, a German neurologist who also described the condition in a separate study. 

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