- Last edited on February 4, 2022
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geri:dementia:creutzfeldt-jakob-disease-cjd [on June 2, 2019] |
geri:dementia:creutzfeldt-jakob-disease-cjd [on February 4, 2022] psychdb [Cerebrospinal Fluid] |
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====== Creutzfeldt-Jakob Disease (CJD) ====== | ====== Creutzfeldt-Jakob Disease (CJD) ====== | ||
+ | {{INLINETOC}} | ||
===== Primer ===== | ===== Primer ===== | ||
- | **Creutzfeldt-Jakob Disease** (CJD) is a rare, fatal, progressive neurodegenerative disorder. It affects about 1 in every 1 million people per year worldwide. CJD has a rapid course and usually appears in late life. There is a very short survival time, death usually occurs within one year of symptom onset. | + | **Creutzfeldt-Jakob Disease** (CJD) is a rare, fatal, [[geri:dementia:0-rapid-rpd|rapidly progressive dementia]]. It affects about 1 in every 1 million people per year worldwide. CJD has a rapid course and usually appears in late life. There is a very short survival time, death usually occurs within one year of symptom onset. |
== Prevalence == | == Prevalence == | ||
- | There approximately 1 or 2 cases per million people. The peak age for the sporadic CJD is 67 years. | + | * There are approximately 1 or 2 cases per million people. |
+ | * The peak age for the sporadic CJD is 67 years. | ||
+ | * Individuals with iatrogenic (iCJD) and variant (vCJD) tend to be much younger | ||
+ | == Prognosis == | ||
+ | * The disease is fatal, and 90% will die within 1 year.[([[https://pubmed.ncbi.nlm.nih.gov/15361416/|Pocchiari, M., Puopolo, M., Croes, E. A., Budka, H., Gelpi, E., Collins, S., ... & Will, R. G. (2004). Predictors of survival in sporadic Creutzfeldt–Jakob disease and other human transmissible spongiform encephalopathies. Brain, 127(10), 2348-2359.]])][([[https://pubmed.ncbi.nlm.nih.gov/32614136/|Llorens, F., Rübsamen, N., Hermann, P., Schmitz, M., Villar‐Piqué, A., Goebel, S., ... & Zerr, I. (2020). A prognostic model for overall survival in sporadic Creutzfeldt‐Jakob disease. Alzheimer's & Dementia, 16(10), 1438-1447.]])] | ||
+ | * End-stage sCJD is generally characterized by [[teaching:apathy|akinetic mutism]]. | ||
+ | * Spasticity and myoclonus become highly prevalent and some patients develop seizures. | ||
===== Classification ===== | ===== Classification ===== | ||
Major or mild neurocognitive disorder (NCD) due to prion disease includes the group of subacute spongiform encephalopathies including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, kuru, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. | Major or mild neurocognitive disorder (NCD) due to prion disease includes the group of subacute spongiform encephalopathies including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, kuru, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. | ||
- | ===== Diagnostic Criteria ===== | + | The most common subtypes of Creutzfeldt-Jakob disease are: |
- | <WRAP group> | + | * **Sporadic (sCJD)**, origin not known, but not thought to be acquired (85-95%) |
- | <WRAP half column> | + | * **Genetic (gCJD)**, mutations of the gene encoding prion protein that area genetically passed on (5-15%) |
+ | * **Iatrogenic (iCJD)**, current practices have essentially eliminated this type; previously caused by cadaveric human pituitary hormones, dural graft transplants, corneal graft transplants (<1%) | ||
+ | * **Variant (vCJD)**, a distinct, acquired prion disease, related to a single bovine prion strain responsible for BSE has infected humans to cause vCJD (<1%) | ||
+ | ===== DSM-5 Diagnostic Criteria ===== | ||
== Criterion A == | == Criterion A == | ||
The criteria are met for [[cl:2-major-neurocog-disorder|major]] or [[cl:3-mild-neurocog-disorder|mild neurocognitive disorder]]. | The criteria are met for [[cl:2-major-neurocog-disorder|major]] or [[cl:3-mild-neurocog-disorder|mild neurocognitive disorder]]. | ||
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== Criterion B == | == Criterion B == | ||
There is insidious onset, and rapid progression of impairment is common. | There is insidious onset, and rapid progression of impairment is common. | ||
- | |||
- | </WRAP> | ||
- | <WRAP half column> | ||
== Criterion C == | == Criterion C == | ||
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== Criterion D == | == Criterion D == | ||
The neurocognitive disorder is not attributable to another medical condition and is not better expiated by another mental disorder. | The neurocognitive disorder is not attributable to another medical condition and is not better expiated by another mental disorder. | ||
- | </WRAP> | + | |
- | </WRAP> | + | ==== Signs and Symptoms ==== |
- | ===== Symptoms ===== | + | CJD should always be considered in a patient with the combination of the ''2'' cardinal clinical features: |
- | CJD should always be considered in a patient with the combination of the two cardinal clinical features: | + | - **Rapid, progressive mental deterioration** including dementia and behavioural abnormalities. Poor concentration, memory, hypersomnia and [[sleep:2-insomnia-disorder|insomnia]], and poor judgment may be early signs. Psychiatric symptoms including depression, apathy, anxiety, and visual hallucinations[([[https://pubmed.ncbi.nlm.nih.gov/18982039/|Proulx, A. A., Strong, M. J., & Nicolle, D. A. (2008). Creutzfeldt-Jakob disease presenting with visual manifestations. Canadian Journal of Ophthalmology, 43(5), 591-595.]])] may also occur. |
- | - **Rapid, progressive mental deterioration** including dementia and behavioural abnormalities. Concentration, memory, and poor judgment may be early signs. Psychiatric symptoms including depression, apathy, and anxiety may also occur. | + | - **Myoclonus and abnormal movements** (including ataxia, chorea, or dystonia). A myoclonus provoked by startle reflex is also common. [[https://www.youtube.com/watch?v=c0IYpOLWdSU|Startle myoclonus]] is present in almost all patients at some point during the disease course. |
- | - **Myoclonus and abnormal movements** (including ataxia, chorea, or dystonia). A myoclonus provoked by startle reflex is also common. Myoclonus, especially provoked by startle (hyperekplexia), is present almost all patients at some point during the disease course. | + | |
===== Pathophysiology ===== | ===== Pathophysiology ===== | ||
- | CJD is caused by transmissible agents known as prions. The most common type is sporadic Creutzfeldt-Jakob disease (sCJD). Variant CJD (vCJD) is much rarer and is associated with transmission of bovine spongiform encephalopathy, also known as "Mad Cow disease." There is a genetic component in up to 15% of cases of CJD, associated with an autosomal dominant mutation. | + | * CJD is caused by transmissible agents known as prions. Prions are small, infectious, protein-containing particles (PrPSc) that replicate over a period of time, replacing normal prion proteins (PrPC) and leading to neurotoxicity. |
+ | * The most common type is sporadic Creutzfeldt-Jakob disease (sCJD). Variant CJD (vCJD) is much rarer and is associated with transmission of bovine spongiform encephalopathy, also known as "Mad Cow disease." There is a genetic component in up to 15% of cases of CJD, associated with an autosomal dominant mutation. | ||
===== Investigations ===== | ===== Investigations ===== | ||
==== Neuroimaging ==== | ==== Neuroimaging ==== | ||
- | Prion disease is diagnosed with least one of the characteristic biomarker features: cortical ribboning or lesions on [[neurology:investigations:neuroimaging:mri|magnetic resonance imaging]] with DWI (diffusion-weighted imaging)[([[https://www.ncbi.nlm.nih.gov/pubmed/26238299|Abdulmassih, R., & Min, Z. (2016). An ominous radiographic feature: cortical ribbon sign. Internal and emergency medicine, 11(2), 281-283.]])] or FLAIR (fluid-attenuated inversion recovery). | + | * Prion disease is diagnosed with least one of the characteristic biomarker features: cortical ribboning or lesions on [[neurology:mri|magnetic resonance imaging]] with DWI (diffusion-weighted imaging)[([[https://www.ncbi.nlm.nih.gov/pubmed/26238299|Abdulmassih, R., & Min, Z. (2016). An ominous radiographic feature: cortical ribbon sign. Internal and emergency medicine, 11(2), 281-283.]])] or FLAIR (fluid-attenuated inversion recovery). |
+ | * MRI typically shows abnormal hyperintense signal in the putamen and head of the caudate as well. | ||
- | ==== Cerebrospinal Fluid ==== | + | ==== Cerebrospinal Fluid (CSF) ==== |
- | Tau or 14-3-3 protein in [[neurology:investigations:lp|cerebrospinal fluid]] can be used to discriminate CJD from other neurodegenerative diseases.[([[https://www.ncbi.nlm.nih.gov/pubmed/16633900|Satoh, K., Shirabe, S., Eguchi, H., Tsujino, A., Eguchi, K., Satoh, A., ... & Matsuo, H. (2006). 14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan. Cellular and molecular neurobiology, 26(1), 45-52.]])] | + | * Tau or 14-3-3 protein in [[neurology:lumbar-puncture-lp|cerebrospinal fluid]] can be used to discriminate CJD from other neurodegenerative diseases.[([[https://www.ncbi.nlm.nih.gov/pubmed/16633900|Satoh, K., Shirabe, S., Eguchi, H., Tsujino, A., Eguchi, K., Satoh, A., ... & Matsuo, H. (2006). 14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan. Cellular and molecular neurobiology, 26(1), 45-52.]])] |
+ | * It is important to note that 14-3-3 and tau is a non-specific finding for CJD. | ||
+ | * Real-time quaking-induced conversion (RT-QuIC), also called protein misfolding cyclic amplification (PMCA) is the most sensitive and specific test for diagnosing sporadic CJD. | ||
==== EEG === | ==== EEG === | ||
- | Characteristic triphasic waves can be seen on [[neurology:investigations:eeg|electroencephalogram]]. | + | * Characteristic triphasic waves and periodic sharp-and-slow (discharges) wave complexes can be seen on [[neurology:eeg|electroencephalogram]].[([[https://pubmed.ncbi.nlm.nih.gov/14744571/|Fernández-Torre, J. L., Solar, D. M., Astudillo, A., Cereceda, R., Acebes, A., & Calatayud, M. T. (2004). Creutzfeldt-Jakob disease and non-convulsive status epilepticus: a clinical and electroencephalographic follow-up study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 115(2), 316–319.]])] |
+ | * Periodic sharp wave complexes have high specificity for CJD but low sensitivity (i.e. - even if absent cannot rule out CJD) | ||
+ | |||
+ | ==== Pathology ==== | ||
+ | * The gold standard diagnosis for CJD is neuropathologic examination (i.e. - brain biopsy) | ||
+ | ===== Physical Exam ===== | ||
+ | <alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success"> | ||
+ | See main article: **[[neurology:neuro-exam:home|]]** | ||
+ | </alert> | ||
+ | * Myoclonus is present in >90% of patients at some point, but is often absent at presentation | ||
+ | * Nystagmus and ataxia can occur in up to half of all patients | ||
+ | * [[https://www.youtube.com/watch?v=c0IYpOLWdSU|Startle myoclonus]] is present in almost all patients at some point during the disease course. | ||
+ | * Hyperreflexia, upper motor neuron signs such as the Babinski sign, and spasticity may be present | ||
+ | * Extrapyramidal signs including hypokinesia, bradykinesia, dystonia, and rigidity may occur. | ||
+ | |||
+ | ===== Differential Diagnosis ===== | ||
+ | <alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success"> | ||
+ | See main article: **[[geri:dementia:0-rapid-rpd|]]** | ||
+ | </alert> | ||
+ | <alert type="info" icon="fa fa-book fa-lg fa-fw"> | ||
+ | See also: **[[https://onlinelibrary.wiley.com/doi/full/10.1002/ana.22454|Chitravas, N., Jung, R. S., Kofskey, D. M., Blevins, J. E., Gambetti, P., Leigh, R. J., & Cohen, M. L. (2011). Treatable neurological disorders misdiagnosed as Creutzfeldt‐Jakob disease. Annals of neurology, 70(3), 437-444.]]** | ||
+ | </alert> | ||
+ | * A consideration of other causes of rapidly progressive dementias should be considered (see article above) | ||
+ | * It is important to recognize that EEG has low sensitivity for CJD, and the non-specificity of CSF protein 14-3-3 elevation for CJD as well. | ||
+ | * One study found that up to 25% of cases diagnosed as sporadic CJD were actually other conditions, including: Alzheimer's disease, vascular dementia, frontotemporal lobar degeneration, mesial temporal sclerosis, and diffuse Lewy body dementia.[([[https://pubmed.ncbi.nlm.nih.gov/21674591/|Chitravas, N., Jung, R. S., Kofskey, D. M., Blevins, J. E., Gambetti, P., Leigh, R. J., & Cohen, M. L. (2011). Treatable neurological disorders misdiagnosed as Creutzfeldt‐Jakob disease. Annals of neurology, 70(3), 437-444.]])] | ||
+ | * A non-exhaustive list from this pathological study of disorders misdiagnosed as CJD include: [[geri:dementia:alzheimers|Alzheimer's disease]], [[geri:dementia:vascular|vascular dementia]], [[geri:dementia:lewy-body|dementia with Lewy bodies]], [[geri:dementia:frontotemporal|frontotemporal degeneration (FTD)]], [[geri:parkinsons|Parkinson's disease]], [[geri:dementia:corticobasal-degeneration-cbd|corticobasal degeneration]], corticostriatonigral degeneration, [[geri:dementia:progressive-supranuclear-palsy-psp|progressive supranuclear palsy]], [[geri:dementia:als|motor neuron disease]], [[cl:huntingtons-disease|Huntington disease]], hereditary ataxia, familial spastic paraplegia, encephalitis - undiagnosed, [[cl:thyroid-disorders:hashimotos|Hashimoto encephalopathy]], [[cl:paraneoplastic-disorders|immune-mediated or paraneoplastic encephalopathy]], vasculitis, brain tumour, metastatic encephalopathy, primary CNS lymphoma, chronic epilepsy, [[cl:multiple-sclerosis|multiple sclerosis]], leukoencephalopathy, metabolic disorder, alcohol-induced atrophy, psychiatric disorders, and unclassified dementia.[([[https://pubmed.ncbi.nlm.nih.gov/21674591/|Chitravas, N., Jung, R. S., Kofskey, D. M., Blevins, J. E., Gambetti, P., Leigh, R. J., & Cohen, M. L. (2011). Treatable neurological disorders misdiagnosed as Creutzfeldt‐Jakob disease. Annals of neurology, 70(3), 437-444.]])] |