Sporadic Creutzfeldt-Jakob Disease (sCJD)

Diseases, ,

Diagnosis:

A type of transmissible spongiform encephalopathy TSE
Clinical +/-EEG +/-MRI +/-CSF findings +/-brain biopsy

Clinical features:

Rapidly progressive, death usually <1 year
Dementia (rapidly progressive), ataxia, myoclonus, rigidity, visual disturbances
Focal cortical symptoms (aphasia, neglect, apraxia, acalculia)
Akinetic mutism (late feature)
Heidenhain variant:

  • Visual symptoms: perception difficulties (colours & structures e.g. metamorphopsia/dysmorphopsia), optical hallucinations, cortical blindness & Anton syndrome (optical anosognosia)
  • Signs:
    • Balint syndrome (simultagnosia, optic apraxia, oculomotor apraxia)
    • Anton syndrome (optical anosognosia)

Findings on Investigations:

MRI, T2 or FLAIR or DW1 or proton density:

  • May be normal
  • Caudate & putamen: hyperintensity (compared with the cortex).
  • Cortical gyral hyperintensity (gyriform) especially on FLAIR, also transient DWI: May be the only finding. Occipital cortex e.g. Heidenhain variant. Subtle cortical atrophy can occur. Also associated with VV1 subtype CJD
  • -Thalamic Pulvinar hyperintensity “pulvinar sign” may occur (more common in variant CJD)
  • Normal T1, and no enhancement post contrast
  • Normal white matter, usually

EEG:

  • Periodic sharp wave complexes PSWC, these are synchronus, 1-2 Hz: may be negative
  • Diffuse slowing: later in the disease
  • Non specific changes in some types

CSF:

  • 14-3-3 protein increased in many subtypes including VV1 subtype: false positives occur
  • No inflammatory cells, sometimes increased protein
  • Tau in CSF: increased >1,300 pg/mL
  • S100b: increased
  • NSE: increased

SPECT: non-specific, hypoperfusion
PET: non-specific, hypometabolism

Pathology and Brain biopsy:

Affects: various areas of the cortex. Occipital in Heidenhain variant, basal ganglia in cases with (rigidity, athetosis, tremor). Minimal gross atrophy
H&E: Spongiform (vacuolar) changes & astrocytic gliosis & granular cell (nerve cell) loss.
Immunohistochemistry: antibody to PrP (amino acid 138 & 152)
Skeletal muscle or spleen western blott for PrP by very sensitive techniques: positive

Classification :

Prion protein PrP western blot migration patterns : type 1 or type 2
PRNP gene chr. 20p codon 129 status : either methionine M or valine V.
Subtypes MM1, MV1, VV1, MM2, MV2, VV2.

Treatment:

Supportive care

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