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 neuroanatomical localization 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.