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. The vast majority are sporadic, but familial and acquired forms are also occasionally encountered. 

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

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

  • sporadic (sCJD)
    • accounts for 85-90% of cases
    • further divided into numerous subtypes according to molecular markers (see pathology section below)
  • variant (vCJD)
    • bovine-to-human transmission of bovine spongiform encephalopathy (a.k.a. "mad cow disease"): considered zoonotic by some
    • especially if in the UK between 1981-1996
    • subsequent human-to-human transmission (e.g. transfusion) of vCJD
  • familial (fCJD)
    • 10% of cases
    • these individuals carry a PRPc mutation
  • iatrogenic (iCJD)
    • following administration of cadaveric human pituitary hormones (pre-1985)
    • various transplants

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. Cerebellar symptoms may often be prominent and early in patients with iCJD secondary to cadaveric human pituitary hormones.

Additionally, various distinct clinical patterns have been linked to various molecular subtypes (e.g. Heidenhain variant linked to MM1 and MM2C 18, and Brownell-Oppenheimer variant linked to VV2 19,20).

  • characteristic results on electroencephalography (EEG)
  • S100
  • CSF 14-3-3 protein: positive result in patient suspected clinically of having sCJD
  • CSF and/or olfactory mucosa real time quaking-induced conversion (RT-QuIC) seeding assays: detects minute amounts of the disease-specific pathologic prion protein 12,13
    • found to be more sensitive than CSF 14-3-3 protein titers 12

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

CJD is thought to be mediated via prions, a type of protein, which manifests in sheep as the disease scrapie, and in cows as bovine spongiform encephalopathy. Prions are considered infectious in the 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.

A number of subtypes of sporadic CJD are recognized based on molecular markers, and these have distinct clinical and pathological features. The classification is based on 16,17:

  • codon 129 in the prion protein gene
    • methionine (M) or valine (V) 
  • size of the protease-resistant core of the abnormal prion protein
    • PrPSc type 1 (21 kDa) or type 2 (19 kDa) 

Each variant of sporadic CJD results from the combination of codon 129 genotype (M or V) and PrPSc type (1, 2 or 1 + 2) 16,17

Additionally, MM2 subtype as has been noted to have distinctive histopathological features affecting the cerebral cortex and the thalamus and have therefore been separated into MM2 cortical (MM2C) and MM2 thalamic (MM2T).

Mixed types are also encountered. The result is that there is significant variation in the literature in regards to how many subtypes there are and if and how they should be grouped together 17.

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.

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

Creutzfeldt-Jakob disease is a notifiable disease in most countries, including European Union countries, Australia, United Kingdom, USA, and Canada.

It was named after Hans Gerhard Creutzfeldt (1885-1964), a German neurologist who first described the condition in 1920, and Alfons Maria Jakob (1884-1931), a German neurologist who also described the condition in a separate study in 1921 14,15

MRI imaging features overlap with many other conditions but the presentation will be different 10,11:

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

Infections of the central nervous system

Article information

rID: 7269
Tag: cjd
Synonyms or Alternate Spellings:
  • Creutzfeld-Jakob disease
  • CJD
  • vCJD
  • sCJD
  • fCJD
  • iCJD

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