Psych · Consultation-liaison psychiatry
Prion disease (CJD) and rapidly progressive dementias
Also known as Creutzfeldt-Jakob disease · CJD · Sporadic CJD · Variant CJD · Iatrogenic CJD · Genetic prion disease · Gerstmann-Straussler-Scheinker syndrome · Fatal familial insomnia · Transmissible spongiform encephalopathy · Rapidly progressive dementia · Heidenhain variant · Cortical ribboning · Pulvinar sign · RT-QuIC
Exam-exhaustive fellowship topic on prion disease and rapidly progressive dementia — sporadic, genetic, iatrogenic and variant CJD; the psychiatric prodrome that reaches psychiatry first; the treatable-causes-first RPD algorithm; MRI cortical ribboning, striatal and pulvinar signs; EEG periodic sharp wave complexes; CSF 14-3-3 and RT-QuIC performance; diagnostic tiers; disclosure, genetic counselling and infection-control duties; prognosis and the palliative phase. FRANZCP-primary, globally tagged.
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Red flags
- Cognitive decline measured in weeks with a date the family can name — rapidly progressive dementia until proven otherwise, not depression
- Myoclonus, ataxia or cortical visual failure in a patient referred as 'agitated depression' — examine, do not just prescribe
- Diagnosing CJD on a positive CSF 14-3-3 alone — the single most cited misdiagnosis in the prion literature
- Excluding CJD on a negative EEG or on an MRI performed without DWI and ADC sequences
- Missing autoimmune encephalitis, CNS lymphoma, neurosyphilis, thyroid disease or B12 deficiency because CJD was assumed first
- Telling a family it is definitely CJD before the treatable work-up is complete
- Disclosing genetic prion risk to relatives without consent, counselling or a clinical genetics pathway
- Forgetting the neurosurgical instrument and surveillance-notification duties once prion disease is suspected
Meet the patient
A 63-year-old accountant is referred to old-age psychiatry as "agitated depression, poor response to sertraline". His wife gives you a date: the second week of March. Before that he did the tax returns. Since then he has stopped driving, cannot find the kitchen, and jumps when the door bangs.[5][11]
On examination he is not slowed by depression; he is ataxic, and when you clap he gives a brief, shock-like whole-body jerk. Ten weeks ago he was well.[1][12]
Every registrar's instinct is to swap the antidepressant. The examiner's question is: "What is the tempo, and what have you excluded?" That question is this whole topic.[11][12]
References20ShowHide
- [1]Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease Brain, 2009.PMID 19773352
- [2]Hermann P, Appleby B, Brandel JP, et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease Lancet Neurol, 2021.PMID 33609480
- [3]Watson N, Brandel JP, Green A, et al. The importance of ongoing international surveillance for Creutzfeldt-Jakob disease Nat Rev Neurol, 2021.PMID 33972773
- [4]Ladogana A, Puopolo M, Croes EA, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada Neurology, 2005.PMID 15883321
- [5]Appleby BS, Rincon-Beardsley TD, Appleby KK, et al. Initial diagnoses of patients ultimately diagnosed with prion disease J Alzheimers Dis, 2014.PMID 24934543
- [6]Zeidler M, Johnstone EC, Bamber RW, et al. New variant Creutzfeldt-Jakob disease: psychiatric features Lancet, 1997.PMID 9314868
- [7]Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK Lancet, 1996.PMID 8598754
- [8]Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease Lancet, 2000.PMID 10791525
- [9]Brown P, Brandel JP, Sato T, et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment Emerg Infect Dis, 2012.PMID 22607808
- [10]Mead S, Hermann P, Mok TH, et al. Genetic causes and modifiers of prion diseases Lancet Neurol, 2026.PMID 41579904
- [11]Day GS Rapidly Progressive Dementia Continuum (Minneap Minn), 2022.PMID 35678409
- [12]Chitravas N, Jung RS, Kofskey DM, et al. Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease Ann Neurol, 2011.PMID 21674591
- [13]Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis Lancet Neurol, 2016.PMID 26906964
- [14]Vitali P, Maccagnano E, Caverzasi E, et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias Neurology, 2011.PMID 21471469
- [15]Steinhoff BJ, Zerr I, Glatting M, et al. Diagnostic value of periodic complexes in Creutzfeldt-Jakob disease Ann Neurol, 2004.PMID 15449324
- [16]Muayqil T, Gronseth G, Camicioli R Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology Neurology, 2012.PMID 22993290
- [17]Foutz A, Appleby BS, Hamlin C, et al. Diagnostic and prognostic value of human prion detection in cerebrospinal fluid Ann Neurol, 2017.PMID 27893164
- [18]Pocchiari M, Puopolo M, Croes EA, et al. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies Brain, 2004.PMID 15361416
- [19]Williams RT, White N, Kearns J, et al. Palliative care symptoms of people living with rapidly progressive prion diseases: a systematic review BMC Palliat Care, 2026.PMID 42046045
- [20]Stevenson M, Uttley L, Oakley JE, et al. Interventions to reduce the risk of surgically transmitted Creutzfeldt-Jakob disease: a cost-effective modelling review Health Technol Assess, 2020.PMID 32122460