Encephalitis and CJD! – 8/22/18

Thanks to Joe for presenting the case of an elderly man presenting with subacute onset of AMS, vision changes, and ataxia, found to have creutzfeldt jakob disease (CJD).


Clinical Pearls

  • Rapidly progressive encephalitis should trigger prion disease, paraneoplastic encephalitis, or Whipple’s!
  • Most common malignancies associated with paraneoplastic encephalitis are SCLC, testicular tumors, thymomas, breast cancer, and hodgkin lymphoma
  • >90% of cases of CJD are sporadic
  • Definitive diagnosis of CJD is made by brain biopsy.  CSF testing of 14-3-3 protein marker and the RT-QuIC protein assay combined have sensitivity and specificity >90%.
  • If prion diseases are on your differential, be sure to let infection control know before doing an LP because strict precautions are required to prevent spread of infection!

Encephalitis:

Defined as AMS > 24 hours plus 2 of the following:

  1. Fever
  2. Focal neurologic deficit
  3. Seizure
  4. CSF pleocytosis
  5. Abnormal findings on EEG or neuroimaging

Differential

Capture

Prion diseases:

  • AKA transmissible spongiform encephalopathies
  • Rare, closely related, fatal, neurodegenerative conditions
  • Occur in humans and mammals
  • Result of accumulation of aggregated forms of the prion protein in the CNS
  • >90% are sporadic, the rest are infectious (kuru, variant CJD, and iatrogenic CJD)
    • Iatrogenic mostly resulting from receipt of growth hormone prepared from cadaveric pituitaries and contaminated cadaveric dura mater allografts
    • Sporadic is not transmissible by blood
  • Kuru was the first one recognized to be transmissible and linked to cannibalism among tribes in New Guinea

CJD: 

  • Most prominent clinical feature is disordered cognition
  • Typically, patients also have motor signs, such as ataxia or spasticity, vague sensory problems, or changes in visual perception
  • Myoclonus is common
  • Progressive neurologic decline resulting in death within 6-12 months
  • One in a million
  • Mean age of onset 57 – 62
  • More common in white people (may be ascertainment bias)

Diagnosis:

  • Elevated CSF levels of 14-3-3 are not very sensitive or specific.  Adding RT-QuIC protein assay to the test increases both sensitivity and specificity to >90%.
  • CDC requires the following criteria for diagnosis:
    • Progressive dementia AND
    • 2 of the following: myoclonus, visual or cerebellar disturbance, pyramidal/extrapyramidal dysfunction, akinetic mutism AND
    • Atypical EEG and/or positive 14-3-3 CSF assay  with clinical duration to death <2 years and or typical MRI abnormalities (see nice example here)

Prognosis:

  • Poor, majority die within 1 year
  • No treatment available

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