- Clinical science
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative condition that is caused by misfolded protein particles (prions). Prion diseases are very rare overall. CJD is the most common prion disease in humans. In most cases, no direct cause of CJD can be established. However, there are also familial forms due to gene mutation or acquired forms as prion particles can be transmitted between individuals, making CJD an infectious disease. Accumulation of prion particles in the brain eventually leads to neuronal degeneration and clinical onset of the disease. The cardinal symptoms of CJD are rapidly progressive dementia and myoclonus. Most patients die within 12 months following disease manifestation. Imaging, EEG, and cerebrospinal fluid (CSF) tests provide diagnostic evidence, although a definite diagnosis can only be made via biopsy or autopsy. To date, no curative treatment is available.
- CJD is the most common prion disease in humans.
Epidemiological data refers to the US, unless otherwise specified.
CJD is divided into three different types:
- Sporadic: (∼ 85%): no identifiable cause
- Familial: (∼ 10–15%): various mutations in the PRNP gene
- Acquired (< 1%)
- CJD is caused by “infectious” prions (PrPSc) that are usually produced endogenously but may also be acquired (see “Etiology”).
- PrPSc → conformational change of physiological PrPc → formation of condensation centers + PrPSc accumulation → plaque formation; → neuronal cell death → progression to spongiform encephalopathy (seen as intracytoplasmic vacuoles within the neurons of cerebral and cerebellar cortex on H&E)
- Latency period varies greatly, but ∼ 10 years is common and ≥ 30 years has been recorded
- Prodromal symptoms (nonspecific): e.g., sleep disorders, headaches, fatigue
- Rapidly progressing dementia
- Other neuropsychiatric symptoms: e.g., visual hallucinations, depression
- Myoclonus: can often be triggered by startling (e.g., loud noises)
- Cerebellar disturbances (e.g., gait instability) and extrapyramidal deficits
- Akinetic mutism
- Autonomic problems (e.g., sweating)
- CSF analysis: neuron‑specific enolase, S100 protein, tau protein, 14-3-3 protein
- Imaging: MRI
- EEG: triphasic periodic sharp wave complexes with a frequency of 1–2 Hz
- Brain biopsy: Diagnosis can only be confirmed by biopsy/autopsy and subsequent neuropathological examination.