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Creutzfeldt-Jakob disease (CJD)

Summary

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  • Rare, fatal neurodegenerative disorder characterised by rapidly progressive dementia
  • Caused by abnormal prion protein accumulation in the brain
  • Imaging findings include cortical ribboning and basal ganglia hyperintensities on DWI/FLAIR1

Pathophysiology

  • Accumulation of abnormally folded prion proteins (PrPSc) in the brain
  • Leads to neuronal loss, gliosis, and spongiform changes
  • Four subtypes:
    1. Sporadic (sCJD): Most common (85-90% of cases)
    2. Familial (fCJD): Genetic mutations in PRNP gene
    3. Iatrogenic (iCJD): Transmission via contaminated medical procedures
    4. Variant (vCJD): Linked to bovine spongiform encephalopathy (BSE)

Demographics

  • Incidence: 1-2 cases per million population per year
  • Median age of onset:
    • sCJD: 60-65 years
    • vCJD: 26-28 years
  • No gender predilection
  • Geographical distribution: Worldwide, with higher incidence in some countries due to genetic factors

Diagnosis

  • Clinical presentation:
    • Rapidly progressive dementia
    • Myoclonus
    • Visual disturbances
    • Cerebellar ataxia
  • Diagnostic criteria:
    1. WHO criteria for probable CJD
    2. MRI findings
    3. CSF biomarkers (14-3-3 protein, tau protein, RT-QuIC)
    4. EEG: Periodic sharp wave complexes
  • Definitive diagnosis: Brain biopsy or post-mortem examination

Imaging

  • MRI:
    • DWI/FLAIR:
    • Cortical ribboning (high signal in cortical grey matter)
    • Basal ganglia hyperintensities (caudate and putamen)
    • Thalamic hyperintensities (pulvinar sign in vCJD)
    • T2-weighted:
    • Subtle hyperintensities in affected areas
  • CT:
    • Generally normal in early stages
    • May show cerebral atrophy in advanced cases
  • PET:
    • Hypometabolism in affected cortical regions and basal ganglia
  • SPECT:
    • Reduced perfusion in affected areas

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  • 65-year-old male presented with myoclonus and cognitive impairment.
  • On the initial MRI, rather equivocal DWI hyperintensity in the corpus striatum became obvious 6 months later.

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  • A 71-year-old female developed progressively worsening confusion and visual hallucinations.
  • Cortical ribboning on DWI was most apparent in the left caudate head, frontal lobe and parietal lobe.

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  • A 65-year-old patient presented with rapidly progressive cognitive impairment and cerebellar ataxia.
  • There was diffusion restriction in the striatum and FLAIR hyperintensity, without diffusion restriction, in the pulvinar of the thalami.

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  • Patient with recent onset cognitive impairment.
  • MRI showed asymmetrical extensive cortical ribboning in the parietal, occipital and temporal lobes.

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  • A 60-year-old patient presented following a focal seizure followed by progressively worsening confusion.
  • Imaging showed cortical (and subtle putaminal) diffusion restriction that was more apparent on B3000 than B1000 DWI.
  • RT-QuIC confirmed the diagnosis of CJD.

Treatment

  • No curative treatment; supportive care only. Uniformly fatal, usually within a year

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Paraneoplastic/autoimmune limbic encephalitis Bilateral mesial temporal FLAIR hyperintensity without cortical ribboning; may enhance
Viral encephalitis (HSV) Asymmetric mesial temporal/insular haemorrhagic FLAIR hyperintensity without cortical ribboning
Wernicke's encephalopathy Symmetric T2 hyperintensity of mammillary bodies, periaqueductal grey, and medial thalami
Autoimmune encephalitis Bilateral hippocampal FLAIR hyperintensity; cortical DWI restriction absent

  1. Hermann et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. 2021. The Lancet. Neurology - Open in new tab. ↩