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

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