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ARCHIVED - Creutzfeldt-Jakob Disease, Classic and Variant

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Nationally notifiable since 2000

This section describes the three etiologic subtypes of classic Creutzfeldt-Jakob disease (CJD) (sporadic CJD, iatrogenic CJD and genetic prion diseases) and variant CJD (vCJD)

A: Sporadic Creutzfeldt-Jakob Disease (sCJD)

1.0 National Notification

Definite, probable and possible cases.

2.0 Type of Surveillance

Case-by-case

3.0 Case Classification

3.1 Confirmed case

Neuropathologically and/or immunocytochemically and/or biochemically confirmed, through observation of one or more neuropathologic features (see Box 1) and no evidence of iatrogenic CJD or genetic human prion disease (see Sections B and C).

3.2 Probable case

Routine investigation should not suggest an alternative diagnosis

3.2.1

Rapidly progressive dementia + at least two features of list I + II (see Box 2)

or

3.2.2

Possible CJD + cerebrospinal fluid positive for 14-3-3 by immunoblot + duration < 2 years

3.3 Possible sCJD

Rapidly progressive dementia + two of list I (see Box 2) + duration < 2 years + no electroencephalography (EEG) or atypical EE

4.0 Laboratory Comments

See Sections A.3.1, A3.2, A3.3

5.0 Clinical Evidence

See Sections A 3.1, A 3.2, A 3.3

6.0 ICD Code(s)

6.1 ICD-10 Code

A81.0
Creutzfeldt-Jakob disease

6.2 ICD-9 Code

046.1
Jakob-Creutzfeldt disease

7.0 Comments

N/A

8.0 References

Surveillance Case Definitions for Human Prion Diseases. Retrieved September 2008, from http: http://www.cjd.ed.ac.uk/criteria.htm

Box 1

  1. Spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter
  2. Encephalopathy with prion protein (PrP) immunoreactivity in plaque-like and/or diffuse synaptic and/or patchy/perivacuolar patterns, by examination of tissue either directly or with assistance of capillary transfer from paraffin-embedded tissue (PET) to secondary support (PET blot)
  3. Presence of scrapie-associated fibrils (SAF) by electron microscopy
  4. Presence of protease-resistant PrP by Western blot

Box 2

    1. Myoclonus
    2. Visual disturbances or cerebellar dysfunction (ataxia)
    3. Pyramidal or extrapyramidal features
    4. Akinetic mutism
  2. Typical EEG pattern: periodic sharp-wave complexes ca. 1 Hz

B: Latrogenic CJD (iCJD)

1.0 National Notification

Definite and probable case.

2.0 Type of Surveillance

Case-by-case

3.0 Case Classification

3.1 Definite iCJD

Definite CJD (see Section A, Box 1 for diagnostic criteria) with a recognized risk factor for iatrogenic transmission (see Box 3)

3.2 Probable iCJD

Progressive predominant cerebellar syndrome in a recipient of cadaverically derived human pituitary growth hormone
OR
Probable CJD (see Section A.3.2 for diagnostic criteria) with a recognized risk factor for iatrogenic transmission (see Box 3)

4.0 Laboratory Comments

See Sections B.3.1, B3.2, B3.3

5.0 Clinical Evidence

See Sections B 3.1, B 3.2, B 3.3

6.0 ICD Code(s)

6.1 ICD-10 Code

A81.0
Creutzfeldt-Jakob disease

6.2 ICD-9 Code

046.1
Jakob-Creutzfeldt disease

7.0 Comments

N/A

8.0 References

Surveillance Case Definitions for Human Prion Diseases. Retrieved July 2008, from http: http://www.cjd.ed.ac.uk/criteria.htm

Box 3

Note: Assessment of the relevance of any proposed risk factor to disease causation should take into account the timing of the putative exposure in relation to disease onset, especially where the putative exposure is recent. As well, this list is provisional, as the risks of iatrogenic transmission of prion disease by other routes are currently incompletely understood.

  1. Treatment with human cadaveric pituitary growth hormone, human pituitary gonadotrophin or human dura mater graft
  2. Corneal graft in which the corneal donor has been classified as having a definite or probable prion disease
  3. Neurosurgical exposure to instruments previously used on a patient classified as having definite or probable prion disease

C: Genetic Prion Diseases

1.0 National Notification

Definite and probable case.

2.0 Type of Surveillance

Case-by-case

3.0 Case Classification

3.1 Definite Genetic Human Prion Disease

3.1.1

Definite (pathologically confirmed) prion disease + definite or probable prion disease in a first-degree relative
or

3.1.2

Definite prion disease + pathogenic mutation in prion protein gene (PRNP) (see Box 4)
or

3.1.3

Typical neuropathologic phenotype of Gerstmann-Sträussler-Scheinker disease (GSS)*

3.2 Probable Genetic Prion Disease

3.2.1

Progressive neuropsychiatric disorder + definite or probable prion disease in a first degree relative

OR

3.2.2

Progressive neuropsychiatric disorder + pathogenic mutation in PRNP (see Box 4)

4.0 Laboratory Comments

See Sections C 3.1, C 3.2, C 3.3

5.0 Clinical Evidence

See Sections C 3.1, C 3.2, C 3.3

6.0 ICD Code(s)

6.1 ICD-10 Code

A81.0
Creutzfeldt-Jakob disease

6.2 ICD-9 Code

046.1
Jakob-Creutzfeldt disease

7.0 Comments

N/A

8.0 References

Surveillance Case Definitions for Human Prion Diseases. Retrieved July 2008, from http: http://www.cjd.ed.ac.uk/criteria.htm

Box 4

  1. PRNP mutations associated with a neuropathologic phenotype of CJD (see Section A, Box 1): P105T, G114V, R148H, D178N, V180I, V180I+M232R, T183A, T188A, T193I, E196K, E200K, V203I, R208H, V210I, E211Q, M232R; octapeptide repeat insertions (various lengths) and deletion (48 bp)
  2. PRNP mutations associated with a neuropathologic phenotype of GSS (see previous footnote above): P102L, P105L, A117V, G131V, A133V, Y145Stop, H187R, F198S, D202N, Q212P, Q217R, M232T; octapeptide repeat insertions (various lengths)
  3. PRNP mutations associated with a neuropathologic phenotype of Familial Fatal Insomnia (FFI): D178N
  4. PRNP mutations associated with other neuropathologic phenotypes: I138M, G142S, Q160Stop, T188K, T188R, P238S, M232R; octapeptide repeat insertions (various lengths)

*Presence of multicentric PrP-immunoreactive plaques in cerebral and/or cerebellar cortex, with neuron loss and spongiosis. Other large amorphic plaques or neurofibrillary tangles immunoreactive for PrP have been described in subsets of GSS, but these are associated with less frequent PRNP mutations (A117V and F198S). Florid or Kuru plaques are not considered diagnostic for GSS.

D: Variant Creutzfeldt-Jakob Disease(vCJD)

1.0 National Notification

Definite, probable and possible cases.

2.0 Type of Surveillance

Case-by-case

3.0 Case Classification

3.1 Definite vCJD

IA (see Box 5) and neuropathologic confirmation as per pathologic features (see footnote a, Box 5)

3.2 Probable vCJD

I + 4 or 5 criteria of II + IIIA + IIIB (see Box 5)
or
I + IVA

3.3 Possible vCJD

I + 4 or 5 criteria of II + IIIA (see Box 5)

4.0 Laboratory Comments

See Sections D 3.1, D 3.2, D 3.3

5.0 Clinical Evidence

See Sections D 3.1, D 3.2, D 3.3

6.0 ICD Code(s)

6.1 ICD-10 Code

A81.0
Creutzfeldt-Jakob disease

6.2 ICD-9 Code

046.1
Jakob-Creutzfeldt disease

7.0 Comments

N/A

8.0 References

Surveillance Case Definitions for Human Prion Diseases. Retrieved July 2008, from http: http://www.cjd.ed.ac.uk/criteria.htm

Box 5

    1. Progressive neuropsychiatric disorder
    2. Duration > 6 months
    3. Routine investigations do not suggest alternative diagnosis
    4. No history of potential iatrogenic exposure
    5. No evidence of genetic prion disease
    1. Early psychiatric symptomsb
    2. Persistent painful sensory symptomsc
    3. Ataxia
    4. Myoclonus or chorea or dystonia
    5. Dementia
    1. EEG does not show typical appearance of sporadic CJDd (or no EEG performed) in the early stages of the illness
    2. Bilateral pulvinar high signal on magnetic resonance imaging (MRI) scane
    1. Tonsil biopsy positive for prion protein immunoreactivityf
  1. Spongiform change, extensive PrP deposition, florid plaques throughout cerebrum and cerebellum
  2. Depression, anxiety, apathy, withdrawal, delusions
  3. Frank pain and/or dysaesthesia
  4. Generalized triphasic periodic complexes at ca. 1 Hz. Rarely, these may occur in the late stages of vCJD.
  5. Relative to the signal intensity of other deep grey matter nuclei and cortical grey matter
  6. Tonsil biopsy is not recommended routinely or in cases with EEG appearance typical of sporadic CJD, but may be useful in suspect cases in which the clinical features are compatible with vCJD and MRI does not show bilateral pulvinar high signal.

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