Prion disease

1998 WHO revised criteria for sporadic Creutzfeldt-Jakob disease[139]Zoonotic Disease Division of Emerging and other Communicable Diseases Surveillance and Control. Global surveillance, diagnosis and therapy of human transmissible spongiform encephalopathies: report of a WHO consultation. Geneva, Switzerland: WHO; 1998. http://whqlibdoc.who.int/hq/1998/WHO_EMC_ZDI_98.9.pdf

The 1998 WHO revised criteria has many shortcomings. Akinetic mutism, 1 of 4 symptoms highlighted in the criteria, is commonly an end-stage sign of sporadic Creutzfeldt-Jakob disease (CJD), making its inclusion unhelpful for early diagnosis. Furthermore, cerebellar and visual symptoms are listed collectively, although they are distinct in both neuro-anatomical localisation and clinical presentation. Revised diagnostic criteria have now been proposed for several countries.

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2018 CDC diagnostic criteria for Creutzfeldt-Jakob disease[70]Centers for Disease Control and Prevention. CDC’s Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD). 2018 [internet publication] https://www.cdc.gov/prions/cjd/diagnostic-criteria.html

1. Sporadic CJD

Definite:

• Diagnosed by standard neuropathological techniques; and/or immunocytochemically; and/or Western blot confirmed protease-resistant PrP; and/or presence of scrapie-associated fibrils.

Probable:

• Neuropsychiatric disorder plus positive RT-QuIC in cerebrospinal fluid (CSF) or other tissues

OR

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

  1. Myoclonus

  2. Visual or cerebellar signs

  3. Pyramidal/extrapyramidal signs

  4. 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

• A positive 14-3-3 CSF assay in patients with a disease duration of less than 2 years

• High signal in caudate/putamen on magnetic resonance imaging (MRI) brain scan or at least two cortical regions (temporal, parietal, occipital) either on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR)

AND without routine investigations indicating an alternative diagnosis.

Possible:

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

  1. Myoclonus

  2. Visual or cerebellar signs

  3. Pyramidal/extrapyramidal signs

  4. Akinetic mutism

AND the absence of a positive result for any of the four tests above that would classify a case as 'probable'

AND duration of illness less than two years

AND without routine investigations indicating an alternative diagnosis.

MRI-Creutzfeldt-Jakob disease (CJD) consortium criteria for sporadic CJD[66]Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009 Oct;132(Pt 10):2659-68. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759336/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/19773352?tool=bestpractice.com

Current European diagnostic criteria

• Clinical signs: dementia, cerebellar or visual, pyramidal or extrapyramidal, akinetic mutism.

• Tests: periodic polyspike-wave complexes and sharp waves on EEG; 14-3-3 detection in CSF (in patients with a disease duration <2 years); high-signal abnormalities in caudate nucleus and putamen or at least 2 cortical regions (temporal-parietal-occipital) either on diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) sequence.

Probable CJD: 2 clinical signs and at least one positive test result.

Possible CJD: 2 clinical signs and a clinical duration <2 years.