Creutzfeldt–Jakob disease


Creutzfeldt–Jakob disease (CJD) is a condition caused by a prion (infectious protein material that is incorporated to healthy tissue and leads to disease). It is a very rare condition (incidence 1/1.000.000 per year).

Like all other prion diseases (Kuru, Variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann-Straussler-Scheinker Syndrome and Fatal Familial Insomnia), the tissue analysis of patients with CJD shows neuronal loss, proliferation of glial cells, absence of inflammation and a spongiform aspect due to the presence of vacuoles.

CLASSIFICATION & ETIOLOGY:

It may be classified as:

Sporadic CJD (sCJD, ~90% of the cases) – It is believed to occur due to a random error of the metabolism that leads to pathogenic prion formation (conversion of regular cellular prion – PrPC to scrapie prion – PrPSc) on the brain cells. Most of the cases involve people around 60 years of age
Variant CJD (vCJD) – It is the kind that may be associated with the consumption of bovines infected by bovine spongiform encephalopathy. It affects younger patients (~28 years) and has a slower deterioration speed (~14 months) when compared to sCJD (~5 months), with more prominent psychiatric symptoms.
Familial CJD (fCJD) – A mutation on the PRNP gene, located at the short of chromosome 20, causes the production of prions. Other familial prion diseases include Fatal Familial Insomnia (FFI) and Gerstmann-Sträussler-Scheinker disease (GSS).
Iatrogenic CJD (iCJD) – Infection occurs due to procedures, transplants, transfusions and other interventions.

SIGNS AND SYMPTOMS:

Once the first symptoms start, the disease is rapidly progressive (~5 months).

Cognitive and behavioral deterioration that progresses rapidly is a common early feature. Psychiatric symptoms may be present as well.

Myoclonus is also another common feature and it can often be induced by startle.

Extrapyramidal symptoms (such as ataxia) may also be present.

DIAGNOSIS:

It is important to exclude alternative diagnosis (infections, paraneoplastic syndromes, autoimmune conditions, metabolic abnormalities, other dementia types).

MRI may show cortical changes in proton density and DWI, as well as hyper intensity of the head of the caudate and putamen on T2 and FLAIR.

EEG in CJD may show a pattern of biphasic or triphasic periodic synchronous sharp wave complexes (PSWC).

Cerebrospinal fluid analysis may show an increase in tau protein and 14-3-3 protein.

Some patients with prion disease may have detectable prions in their urine. However, urine tests are not yet common diagnostic practice for CJD.

CDC`s DIAGNOSTIC CRITERIA:

1. Sporadic CJD
Definite diagnosis:
Diagnosed by standard neuropathological techniques; and/or immunocytochemically; and/or Western blot confirmed protease-resistant PrP; and /or presence of scrapie-associated fibrils.

Probable diagnosis:
Rapidly progressive dementia; and at least two out of the following four clinical features:

Myoclonus
Visual or cerebellar signs
Pyramidal/extrapyramidal signs
Akinetic mutism
AND a positive result on at least one of the following laboratory tests:

a typical EEG (periodic sharp wave complexes) during an illness of any duration; and/or
a positive 14-3-3 cerebrospinal fluid (CSF) assay in patients with a disease duration of less than 2 years
Magnetic resonance imaging (MRI) high signal abnormalities in caudate nucleus and/or putamen on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR)

AND without routine investigations indicating an alternative diagnosis.

Possible diagnosis:
Progressive dementia; and at least two out of the following four clinical features:

Myoclonus
Visual or cerebellar signs
Pyramidal/extrapyramidal signs
Akinetic mutism

AND the absence of a positive result for any of the three laboratory tests that would classify a case as “probable” (see tests a-c above)
AND duration of illness less than two years
AND without routine investigations indicating an alternative diagnosis.

2. Iatrogenic CJD
Progressive cerebellar syndrome in a recipient of human cadaveric-derived pituitary hormone; or sporadic CJD with a recognized exposure risk, e.g., antecedent neurosurgery with dura mater implantation.

3. Familial CJD
Definite or probable CJD plus definite or probable CJD in a first degree relative; and/or Neuropsychiatric disorder plus disease-specific PrP gene mutation.
The definitive diagnosis requires neuropathological analysis (brain biopsy) showing features of prionic disease.

TREATMENT:

Currently there is no effective treatment for CJD. The medical care should be focused on providing supportive comfort for the patient and family.

REFERENCES & FURTHER READING:

  1. Creutzfeldt-Jakob Disease, Classic (CJD). Centers for Disease Control and Prevention. Page last reviewed: February 6, 2015.
  2. Parchi P et al. Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA. Acta Neuropathol. 2012 Oct;124(4):517-29.
  3. Gambetti P et al. Creutzfeldt–Jakob disease. Encyclopedia of Movement Disorders, Volume 1. 263-269.
  4. National Prion Disease Pathology Surveillance Center.