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Creutzfeldt-Jakob Disease
Aka: Creutzfeldt-Jakob Disease, Jakob-Creutzfeldt Disease, Creutzfeldt Jakob Disease, Jakob Creutzfeldt Disease, Sporadic Jakob-Creutzfeldt Disease, Sporadic Creutzfeldt-Jakob Disease, Sporadic CJD, New Variant Creutzfeldt-Jakob Disease, Variant Creutzfeldt-Jakob Disease, Variant CJD, Iatrogenic Creutzfeldt-Jakob Disease, Familial Creutzfeldt-Jakob Disease, Genetic Creutzfeldt-Jakob Disease
- See Also
- Prion Disease
- Epidemiology
- Incidence of Sporadic CJD: Less than one case per million
- Sporadic Jakob-Creutzfeldt Disease is the most common Prion Disease
- Age of onset: Mean 68 (range: 55-75 years old)
- Causes: Human CJD
- See Prion Disease for Cow vCJD (Bovine Spongiform Encephalopathy, Mad Cow Disease)
- Sporadic Creutzfeldt-Jakob Disease (>80% of U.S. cases, all Sporadic CJD)
- By far, the most common form of Creutzfeldt-Jakob Disease (and the presentation reviewed on this page)
- Genetic Creutzfeldt-Jakob Disease (10-15% of U.S. cases)
- Most cases are familial and represented by 20 different mutations in prion-related protein gene (PRNP)
- Most common PRNP Mutation is E200K (Sephardic Jews in Libya and Tunisia, Slovokians)
- Presents as rapidly progressive Dementia and Ataxia with onset ages 30 to 55 years old
- MRI Findings are similar to that seen in Sporadic Creutzfeldt-Jakob Disease
- Acquired (rare, <1% of U.S. CJD cases)
- Iatrogenic Creutzfeldt-Jakob Disease Causes
- Growth Hormone injections
- Corneal grafts
- Dural grafts
- Neurosurgical equipment
- Blood Transfusion (from donor infected with Variant Jakob-Creutzfeldt Disease)
- Variant Creutzfeldt-Jakob Disease (vCJD)
- Transmission from animals to humans (typically Bovine Spongiform Encephalopathy or BSE)
- Peak in UK BSE cases (1988-2005) followed by tens of thousands of UK cases (1994-2009)
- Since 2012, vCJD cases have been rare
- https://en.wikipedia.org/wiki/United_Kingdom_BSE_outbreak
- Onset in much younger cohort than in Sporadic CJD (mean age onset 27 years old)
- Almost all cases are due to Homozygous PRNP Mutation (methionine at codon 129)
- Unlike other CJD forms, Prion Protein (PrP-Sc) is also found in lymphoreticular tissue (in addition to CNS)
- Presentation
- Initial psychiatric prodrome alone for 6 months
- Cgnitive disorder
- Cerebellar dysfunction and Movement Disorder (e.g. Myoclonus, Chorea)
- Diagnostics
- EEG, CSF and CSF biomarkers are typically non-diagnostic
- EEG will often show non-specific slowing
- MRI DWI shows thalamic hyperintensity with pulvinar sign positive in 75% of cases
- Pulvinar sign is bilateral hyperintensity of medial and posterior Thalamus
- Appears as "double hockey stick sign"
- Zeider (2000) Lancet 355:1412 [PubMed]
- Pathophysiology: Sporadic CJD
- See Prion Disease
- Classification of Sporadic CJD is based on 2 factors
- Prion gene polymorphism (PRNP) at codon 129 with Methionine (M) or Valine (V)
- Prion Protein Size (Type 1 - 21 kDa, Type 2 - 19 kDa)
- Presentations of Sporadic CJD vary based on classification (may have more than one variant)
- Rapidly progression Dementia with Myoclonus and variable Ataxia (40% of cases): MM1, MV1
- Rapidly progressive Ataxia (15% of cases): VV2
- Slower progression of Ataxia or Dementia (8% of cases): MV2
- Sporadic Fatal Familial Insomnia: MM2-Thalamic
- Symptoms: Sporadic CJD
- Constitutional (early prodromal in one third of patients)
- Fatigue
- Headache
- Malaise
- Vertigo
- Altered nutritional intake and Unexplained Weight Loss
- Altered sleep
- Behavioral Changes (early finding in 20-30% or patients)
- Agitation and irritability (36% of cases)
- Depressed Mood
- Anger or agression
- Apathy
- Personality Change
- Memory Loss (40% of patients)
- Sensory Changes (9% of patients)
- Paresthesias
- Pain
- Executive Function Disturbance (early finding in 15%, present in 50% of patients overall)
- Aphasia
- Apraxia
- Neglect
- Acalculia
- Signs: Sporadic CJD
- Rapidly progressive Dementia
- Ataxia (esp. gait disturbance, and other cerebellar signs)
- Myoclonus
- Tremor
- Extrapyramidal signs
- Visual loss, disturbance or oculomotor defects such as Diplopia (7%)
- Labs: Sporadic CJD
- Brain Biopsy
- Amyloidosis
- Gliosis
- Nerve Cell Loss
- Vacuolation (Spongiform change)
- Prion Protein - Scrapie (PrP-Sc) deposition
- Immunohistochemistry or Western Blot
- Protease Resistant Prion Protein - Scrapie (PrP-Sc)
- CSF
- Typically normal (although CSF Protein may be mildly increased)
- CSF biomarkers (14-3-3, D100B, NSE, t-tau) have variable efficacy
- Diagnostics: Sporadic CJD
- EEG (later findings)
- Slow wave background
- High voltage spikes at 1-2 Hz (may be biphasic or triphasic)
- Imaging: Sporadic CJD
- Brain MRI (diffusion weighted or DWI)
- Cortical or deep nuclei gray matter with restricted diffusion
- High Test Sensitivity (92-96%) and high Test Specificity (93-94%)
- Abnormal Hyperintensity (FLAIR imaging)
- Cortical gyri
- Caudate
- Putamen
- Thalamus
- Resources
- CJD Foundation
- http://www.cjdfoundation.org
- Prognosis: Sporadic CJD
- Rapidly progressive neurogenerative condition with short-term mortality approaching 100%
- Mean survival: 6 months (90% mortality within 1 year)
- References
- Belay (2001) Arch Neurol 58:1673-8 [PubMed]
- Brown (2000) Neurology 55(8):1075-81 [PubMed]
- Drisko (2002) J Am Coll Nutr 21(1):22-5 [PubMed]
- Geschwind (2015) Continuum 21(6): 1612-38 +PMID:26633779 [PubMed]