Makindo Medical Notes

Related Subjects: |Dementias |Gerstmann-Straussler-Scheinker Syndrome (GSS) |Fatal Familial Insomnia (FFI) |Creutzfeldt Jakob disease (CJD) |Variant Creutzfeldt Jakob disease (vCJD) |Kuru

About

• The classical form of Creutzfeldt-Jakob disease (CJD) is unrelated to bovine spongiform encephalopathy (BSE).
• Affects older patients and has a more aggressive course compared to the variant form.

Types

• Most cases of CJD are sporadic.
• 5-15% are familial, with autosomal dominant inheritance.
• Iatrogenic cases are due to exposure through medical procedures (e.g., pituitary extracts for GH, corneal transplants, dura mater implantation).

Diagnostic Criteria

• Definite
  • Confirmed by standard neuropathological techniques, immunocytochemistry, or Western blot for protease-resistant prion protein (PrP).
  • Presence of scrapie-associated fibrils can also confirm diagnosis.
• Probable
  • Neuropsychiatric disorder with positive real-time quaking-induced conversion (RT-QuIC) in cerebrospinal fluid (CSF) or other tissues.
  • OR
  • Rapidly progressive dementia with at least two of the following clinical features:
    • Myoclonus
    • Visual or cerebellar signs
    • Pyramidal or extrapyramidal signs
    • Akinetic mutism
  • AND positive findings on one of the following:
    • Typical EEG with periodic sharp wave complexes.
    • CSF positive for protein 14-3-3 within 2 years of disease onset.
    • MRI showing high signal in the caudate/putamen or two cortical regions (temporal, parietal, or occipital) on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR).
• Possible
  • Progressive dementia with at least two of the following four clinical features:
    • Myoclonus
    • Visual or cerebellar signs
    • Pyramidal or extrapyramidal signs
    • Akinetic mutism

Diagram

Clinical and Pathologic Characteristics Distinguishing Classic CJD from Variant CJD

Clinical Presentation

• Rapidly progressive dementia with myoclonus.
• Behavioral changes; diagnosis can be difficult, especially in older patients where cases may be missed.
• The variant form, linked to BSE, affects younger individuals and causes late-onset dementia.

Investigations

• Post-mortem examination shows spongiform changes in the brain, with atrophy in the cerebral cortex, basal ganglia, thalamus, and cerebellum. Amyloid plaques are often present.
• EEG often shows periodic triphasic sharp-wave complexes.
• CSF shows presence of protein 14-3-3, though this may also be seen in multiple sclerosis (MS) and acute stroke.
• MRI shows high signal intensity in the caudate nucleus and putamen bilaterally on T2-weighted images.
• Brain biopsy is the gold standard for diagnosis, with staining for PrP^Sc (scrapie prion protein).

Management

• There is no cure; management is supportive.
• Report suspected cases to the CJD surveillance unit.
• Genetic counseling is recommended for familial cases.