Prion Diseases and Creutzfeldt-Jakob Disease
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Direct answer
Prion diseases are transmissible neurodegenerative disorders caused by misfolded prion protein, which accumulates in the brain and produces spongiform change with little inflammatory response. Creutzfeldt-Jakob disease is the classic human form, presenting as a rapidly progressive dementia over weeks to months with myoclonus, ataxia and visual or cerebellar signs. The most useful clues are periodic sharp wave complexes on EEG, a raised 14-3-3 protein in cerebrospinal fluid and cortical or basal ganglia hyperintensity on diffusion-weighted MRI.
What you must remember
- Commonest form: sporadic CJD is the most frequent type worldwide, presenting in later life with a course usually measured in months.
- Clinical picture: rapidly progressive dementia with myoclonus and cerebellar or visual signs; a dementia that runs its course in months should prompt prion disease rather than Alzheimer disease.
- EEG: periodic sharp wave complexes at about one per second on a slowed background are the classic finding, though they may be absent in variant disease.
- 14-3-3 protein: supportive but not specific, because encephalitis and other rapidly progressive conditions can also raise it; RT-QuIC on CSF is more specific.
- Variant CJD: linked to bovine spongiform encephalopathy exposure, affecting younger patients with psychiatric or sensory onset and a pulvinar sign on MRI.
- Genetics: PRNP mutations on chromosome 20 cause familial CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia; codon 129 genotype modifies susceptibility.
- Infection control: prions resist routine disinfection and autoclaving alone, so handling follows specific WHO and national guidance.
A worked case: rapid memory loss and jerks
A 64-year-old woman develops personality change and memory loss over six weeks, then startle myoclonus and gait ataxia.
- Exclude treatable mimics: A dementia moving this fast should first trigger a search for treatable causes, so thyroid, B12 and sodium estimations are expected alongside MRI and EEG.
- Image the brain: MRI shows diffusion restriction in the cortical ribbon and caudate.
- Confirm with EEG and CSF: EEG shows periodic sharp waves, and the CSF 14-3-3 protein is positive.
- Exclude the main alternative: Autoimmune limbic encephalitis is excluded by antibody testing and the imaging pattern.
- Provide supportive care: Manage myoclonus and falls, involve palliative services early, and ask about family history, since a parent with a similar illness raises the question of a PRNP mutation and genetic counselling.
Because the disease is uncommon, clinicians often reach for familiar causes first, so recognising the pattern early spares the patient and the ward unnecessary delay. Early, honest discussion with the family about the expected course is part of the same duty.
Where the examiner sets the trap
Prion questions usually test which clue is supportive and which is decisive.
- Trap: Treating a positive 14-3-3 result as diagnostic. Correct: 14-3-3 is supportive but not specific, so it must be read against MRI and the clinical course.
- Trap: Excluding CJD because the EEG lacks sharp waves. Correct: In variant disease the EEG is often unhelpful, so absent periodic sharp waves do not exclude the diagnosis.
- Trap: Using routine decontamination after a prion case. Correct: Prions resist routine disinfection and autoclaving alone, so handling follows specific WHO and national guidance.
- Trap: Labelling a young patient with depression as psychiatric alone. Correct: Depression, behavioural change and painful paraesthesiae in a young patient should prompt consideration of variant CJD.
The candidate who names both the rapid time course and the MRI pattern in one sentence usually scores the mark.
Frequently asked questions
Which EEG finding suggests sporadic Creutzfeldt-Jakob disease?
Periodic sharp wave complexes at about one per second on a slowed background are the classic EEG finding in sporadic Creutzfeldt-Jakob disease. Their absence does not exclude the diagnosis, particularly in variant forms, so EEG is one clue among several rather than a standalone test.
Is a raised 14-3-3 protein in CSF diagnostic of Creutzfeldt-Jakob disease?
No, 14-3-3 protein in cerebrospinal fluid is supportive but not specific for Creutzfeldt-Jakob disease. It can be raised in other rapidly progressive conditions such as encephalitis, so a positive result must be interpreted alongside MRI findings and the clinical course.
How does variant Creutzfeldt-Jakob disease differ from the sporadic form?
Variant Creutzfeldt-Jakob disease, linked to exposure to bovine spongiform encephalopathy, affects younger patients who present with psychiatric or sensory symptoms and a longer course. Its MRI often shows a pulvinar hyperintensity, and EEG sharp waves are frequently absent.
Which gene encodes the prion protein in familial prion disease?
The PRNP gene on chromosome 20 encodes the prion protein, and its mutations cause familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. Genetic counselling is offered to relatives when a PRNP mutation is identified in the family.