Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob Disease (CJD) is a rare, fatal, rapidly progressive dementia. It affects about 1 in every 1 million people per year worldwide. CJD has a rapid course and usually appears in late life. There is a very short survival time, death usually occurs within one year of symptom onset.

  • There are approximately 1 or 2 cases per million people.
  • The peak age for the sporadic CJD is 67 years.
    • Individuals with iatrogenic (iCJD) and variant (vCJD) tend to be much younger
  • The disease is fatal, and 90% will die within 1 year.[1][2]
  • End-stage sCJD is generally characterized by akinetic mutism.
    • Spasticity and myoclonus become highly prevalent and some patients develop seizures.

Major or mild neurocognitive disorder (NCD) due to prion disease includes the group of subacute spongiform encephalopathies including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, kuru, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia.

The most common subtypes of Creutzfeldt-Jakob disease are:

  • Sporadic (sCJD), origin not known, but not thought to be acquired (85-95%)
  • Genetic (gCJD), mutations of the gene encoding prion protein that area genetically passed on (5-15%)
  • Iatrogenic (iCJD), current practices have essentially eliminated this type; previously caused by cadaveric human pituitary hormones, dural graft transplants, corneal graft transplants (<1%)
  • Variant (vCJD), a distinct, acquired prion disease, related to a single bovine prion strain responsible for BSE has infected humans to cause vCJD (<1%)
Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

There is insidious onset, and rapid progression of impairment is common.

Criterion C

There are motor features of prion disease, such as myoclonus or ataxia, or biomarker evidence.

Criterion D

The neurocognitive disorder is not attributable to another medical condition and is not better expiated by another mental disorder.

CJD should always be considered in a patient with the combination of the 2 cardinal clinical features:

  1. Rapid, progressive mental deterioration including dementia and behavioural abnormalities. Poor concentration, memory, hypersomnia and insomnia, and poor judgment may be early signs. Psychiatric symptoms including depression, apathy, anxiety, and visual hallucinations[3] may also occur.
  2. Myoclonus and abnormal movements (including ataxia, chorea, or dystonia). A myoclonus provoked by startle reflex is also common. Startle myoclonus is present in almost all patients at some point during the disease course.
  • CJD is caused by transmissible agents known as prions. Prions are small, infectious, protein-containing particles (PrPSc) that replicate over a period of time, replacing normal prion proteins (PrPC) and leading to neurotoxicity.
  • The most common type is sporadic Creutzfeldt-Jakob disease (sCJD). Variant CJD (vCJD) is much rarer and is associated with transmission of bovine spongiform encephalopathy, also known as “Mad Cow disease.” There is a genetic component in up to 15% of cases of CJD, associated with an autosomal dominant mutation.
  • Prion disease is diagnosed with least one of the characteristic biomarker features: cortical ribboning or lesions on magnetic resonance imaging with DWI (diffusion-weighted imaging)[4] or FLAIR (fluid-attenuated inversion recovery).
  • MRI typically shows abnormal hyperintense signal in the putamen and head of the caudate as well.
  • Tau or 14-3-3 protein in cerebrospinal fluid can be used to discriminate CJD from other neurodegenerative diseases.[5]
    • It is important to note that 14-3-3 and tau is a non-specific finding for CJD.
  • Real-time quaking-induced conversion (RT-QuIC), also called protein misfolding cyclic amplification (PMCA) is the most sensitive and specific test for diagnosing sporadic CJD.
  • Characteristic triphasic waves and periodic sharp-and-slow (discharges) wave complexes can be seen on electroencephalogram.[6]
    • Periodic sharp wave complexes have high specificity for CJD but low sensitivity (i.e. - even if absent cannot rule out CJD)
  • The gold standard diagnosis for CJD is neuropathologic examination (i.e. - brain biopsy)
  • Myoclonus is present in >90% of patients at some point, but is often absent at presentation
  • Nystagmus and ataxia can occur in up to half of all patients
  • Startle myoclonus is present in almost all patients at some point during the disease course.
  • Hyperreflexia, upper motor neuron signs such as the Babinski sign, and spasticity may be present
  • Extrapyramidal signs including hypokinesia, bradykinesia, dystonia, and rigidity may occur.