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
- Prion disease
- Alzheimer’s disease (AD)
- Dementia with Lewy bodies (DLB)
- Frontotemporal dementia (FTD)
- Corticobasal syndrome (CBS)
- Progressive supranuclear palsy (PSP)
Systemic
- Sarcoid
- Mitochondrial disease (e.g., MELAS)