Group of rare, uniformly fatal neurodegenerative diseases. In humans they occur in 3 forms: sporadic (85% to 90% of cases), genetic (10% to 15%), and acquired (<1%).
Prions or proteinaceous infectious particles are the misshaped proteins responsible for causing transmissible spongiform encephalopathies, or prion diseases.
Present as very rapidly progressive dementias. Symptoms may vary, but include behavioral/psychiatric changes, memory impairment, visual disturbances, myoclonus, ataxia, language and hearing problems, and movement dysfunction.
Misdiagnosis is common, as Creutzfeldt-Jakob disease (CJD) can present similarly to other neurologic conditions. Pathology currently is the only definitive way to diagnose prion disease, although biopsy and even autopsy may yield false-negative results.
Premortem diagnostic tools that may be helpful include MRI, EEG, and CSF findings, as well as blood tests to rule out other conditions. Brain MRI, particularly diffusion-weighted imaging, has very high sensitivity and specificity for CJD, as does the real-time quaking-induced conversion (RT-QuIC) test on CSF.
Currently, there is no cure for prion disease, and treatment consists of management of symptoms and palliative care. Survival for most sporadic prion patients is generally about 1 year or less, whereas survival of genetic prion disease varies greatly from a few months to several years depending on the mutation.
Prion diseases (or transmissible spongiform encephalopathies) are a group of uniformly fatal neurodegenerative diseases characterized by progressive dementia and motor dysfunction. These diseases occur in spontaneous, genetic, and acquired forms. Patients commonly present with behavioral or personality changes, myoclonus, visual disturbances, movement problems, and/or incoordination. Survival from first symptom is typically <1 year in sporadic and acquired cases.
History and exam
Key diagnostic factors
- cognitive impairment
- limb and/or gait ataxia
- psychiatric symptoms
- visual changes
- age late 20s or mid-to-late 60s
- insomnia, dysautonomia
- positive family history
- nonspecific or constitutional symptoms
Other diagnostic factors
- painful sensory symptoms
- movement disorder
- genetic predisposition
- prion-contaminated surgical instruments
- transfusion of blood or blood products (variant Creutzfeldt-Jakob disease)
- consumption of UK beef from 1980 to 1996
- consumption of US beef
- deer, elk, moose hunting in endemic regions of US and Canada
- use of human growth hormone
1st investigations to order
- brain MRI
Investigations to consider
- quaking-induced conversion (QuIC)
- CSF biomarkers
- prion protein gene genetic testing
- biopsy (brain, tonsil)
- Alzheimer dementia (AD)
- Lewy body dementia
- Frontotemporal dementia
- ACR appropriateness criteria: movement disorders and neurodegenerative diseases
- Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease
- Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer