- SymptomsChanges that progress quickly.
- Neurological examA specialist looks for other causes first.
- MRI and EEGBrain scan and brain wave test.
- Spinal fluid testsIncluding RT-QuIC, where available.
- Specialist reviewCriteria give a probable diagnosis.
- ConfirmationA definite diagnosis needs brain tissue, usually after death.
The order differs by hospital and country.
The steps below are the usual ones. The order can change, and not everyone has every test.
What happens at the first appointments?
Someone is referred to a neurologist, a doctor who specialises in the brain and nervous system. The neurologist takes a history and examines the person. It helps if a relative or friend comes too, because changes in memory, balance, vision or behaviour are often clearer to the people around someone than to the person themselves. Writing down when each change started, in whatever order you remember it, is genuinely useful at this appointment.
Blood tests come first. They look for other causes of the same symptoms, including infections, thyroid problems and vitamin deficiencies, some of which can be treated.
Which tests look for a prion disease?
An MRI scan of the brain, which can show a pattern of changes that doctors associate with these illnesses. Certain scan settings, which the radiologist chooses, show them best.
An EEG, which records the electrical activity of the brain through small pads on the scalp. It is painless. In sporadic CJD it sometimes shows a particular repeating pattern.
A lumbar puncture, where a small amount of the fluid around the spinal cord is taken with a needle in the lower back. The fluid is sent to a national prion laboratory for tests including RT-QuIC, which detects the misfolded prion protein itself, and markers called 14-3-3 and tau, which rise when brain cells are being damaged by any cause. At the United States national centre the laboratory time for these is five working days from the day the sample arrives, and posting and reporting add to that.
A blood test of the prion protein gene, if a relative has had a prion disease or the person is younger than usual, which looks for an inherited change.
Tests explained describes each of these in more detail, and the Atlas tests pages hold the technical records.
Who decides, and what do the words mean?
The local team sends the results to a national specialist service for an opinion. Doctors then use agreed international criteria and the words possible, probable and definite. Probable means the symptoms and the test results together fit a prion disease and nothing else explains them. A single positive RT-QuIC result on spinal fluid, in someone with the right symptoms, is enough for probable on its own.
Definite is kept for cases where brain tissue has been examined. A brain biopsy during life is rarely done, and only when doctors think there may be a different, treatable illness, because the operation carries its own risks. For most families the confirmation, if they want it, comes from examination after death.
A probable diagnosis is the working diagnosis. Care, support and planning do not wait for anything further.
What next
Questions for your doctor is a short list to take to the next appointment. How prion disease is diagnosed: more detail is the fuller version for counsellors and clinicians, and research on diagnostics covers the tests still being developed.
Only the neurologist who ordered the tests can say what one person’s results mean. Questions about a gene in the family belong with a genetic counsellor, before any testing is arranged.