CJD Differential Diagnosis

The disease course of CJD is highly variable and may mimic many other neurological disorders. The first step is to rule out alternative diagnoses.

A diagnosis of probable CJD requires an extensive exclusionary work up. The mnemonic device VITAMINS highlights other potential causes of rapidly progressive dementias:

Vascular
Infectious
Toxic-metabolic
Autoimmune
Metastases/neoplasm
Iatrogenic
Neurodegenerative
Systemic

It is important to rule out these conditions before confirming prion disease.

Vascular

  • Brain angiogram, echocardiogram, carotid ultrasound
  • Hypercoagulability testing, coagulation profile

Infectious

  • Viral encephalitis, including herpes simplex virus
  • HIV dementia
  • Progressive multifocal leukoencephalopathy
  • Subacute sclerosing panencephalitis (young adults)
  • Fungal infections (immunosuppression [e.g., central nervous system (CNS) aspergillosis])
  • Syphilis
  • Lyme disease (rarely encephalopathy)
  • Balamuthia
  • Whipple's disease

Toxic-Metabolic

  • Endocrine abnormalities (thyroid disturbances, parathyroid abnormalities, adrenal diseases)
  • Electrolyte abnormalities (including Ca, Mg, P)
  • Vitamin deficiency (B12[cyanocobalamin], B1 [thiamine], niacine, folate [dementia rare])
  • Uremia
  • Wilson's disease
  • Hepatic encephalopathy
  • Porphyria
  • Bismuth toxicity
  • Metal (lithium, bismuth, lead, mercury, arsenic) toxicity

Autoimmune

  • Hashimoto's encephalopathy (HE)
  • Paraneoplastic (autoimmune) limbic encephalopathy (PLE)
  • Nonparaneoplastic autoimmune (e.g., anti–voltage-gated potassium channel [VGKC] antibodies mediated)
  • Lupus cerebritis
  • Other CNS vasculitides
  • Sarcoid

Metastases/Neoplasm

  • Non-autoimmune paraneoplastic conditions
  • Metastases to CNS
  • Primary CNS lymphoma (PCNSL)
  • Intravascular lymphoma
  • Lymphomatoid granulomatosis
  • Gliomatosis cerebri

Iatrogenic

  • Exposure history
  • Medication use

Neurodegenerative

Systemic

  • Sarcoid
  • Mitochondrial disease (e.g., MELAS)