What are the features of Creutzfeldt-Jakob disease (CJD)?

Features of Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob Disease is characterized by rapidly progressive dementia accompanied by myoclonus, ataxia, and other neurological manifestations, with a universally fatal outcome typically within months of symptom onset. 1

Clinical Presentation

Cardinal Features

• Rapidly progressive dementia (weeks to months)
• Myoclonus (sudden, brief muscle jerks)
• Ataxia (loss of coordination)
• Pyramidal and extrapyramidal signs
• Akinetic mutism in late stages 2, 1

Early Symptoms

• Cognitive deficits (memory loss, confusion)
• Language disturbances (aphasia)
• Personality changes
• Visual disturbances (including hallucinations)
• Psychiatric symptoms (depression, anxiety) 2, 1, 3

Disease Progression

• Typical CJD: Rapid deterioration with median survival of 5 months 2
• Atypical presentations: May have slower progression (up to 11 months) 2
• Terminal phase: Akinetic mutism, loss of all voluntary movement 1

Diagnostic Findings

Cerebrospinal Fluid (CSF) Biomarkers

• RT-QuIC: Highly specific (near 100%) with sensitivity of 73-97% 1
• 14-3-3 protein: Primary surrogate biomarker (elevated)
• Total Tau protein: Significantly elevated (>1300 pg/mL)
• p-Tau/t-Tau ratio: Valuable supportive biomarker 2

Neuroimaging

• MRI findings:
  • DWI/FLAIR: Hyperintensities in cortical regions ("cortical ribboning")
  • Basal ganglia and thalamic hyperintensities
  • Restricted diffusion in caudate nucleus and putamen 2
• CT: Often normal early in disease; progressive atrophy on follow-up 2
• FDG-PET: Widespread cerebral hypometabolism even in early stages 2

Electroencephalography (EEG)

• Periodic sharp wave complexes (PSWCs)
• Triphasic complexes
• Continuous focal epileptiform patterns 2

Genetic Testing

• PRNP gene sequencing: Important to distinguish sporadic from genetic forms
• Codon 129 polymorphism: Influences disease phenotype and progression 2

CJD Subtypes

Sporadic CJD (sCJD)

• Most common form (85% of cases)
• Incidence: 1-2 cases per million annually
• Peak age: 55-75 years 2, 1

Genetic/Familial CJD

• Associated with mutations in the PRNP gene
• Examples include E200K mutation 4
• Family history may be present 2

Iatrogenic CJD

• Transmission through medical procedures
• Risk from contaminated surgical instruments, corneal grafts, dura mater grafts 1

Variant CJD (vCJD)

• Associated with bovine spongiform encephalopathy exposure
• Different clinical presentation (younger age, psychiatric symptoms predominate)
• Risk of transmission through blood transfusion 1

Atypical Presentations

• Stroke-like onset with focal neurological deficits 5, 4
• Corticobasal syndrome variant 4
• Predominant psychiatric presentation (depression, anxiety, OCD) 3, 6
• Heidenhain variant: Visual symptoms predominate 7

Differential Diagnosis

• Other rapidly progressive dementias
• Autoimmune encephalitis
• Status epilepticus
• Cerebral ischemia
• Multiple sclerosis
• Other neurodegenerative disorders (Alzheimer's, frontotemporal dementia) 2, 1

Diagnostic Algorithm

1. Consider CJD in any patient with rapidly progressive dementia (weeks to months)
2. Perform MRI with DWI and FLAIR sequences
3. Obtain CSF for RT-QuIC, 14-3-3 protein, and t-Tau testing
4. Perform EEG to look for characteristic patterns
5. Consider PRNP gene sequencing
6. Rule out treatable causes of rapidly progressive dementia 2, 1

Prognosis

• Universally fatal disease
• Median survival: 5 months from symptom onset
• Most patients die within 1 year of diagnosis 1

Important Caveats

• Early diagnosis is challenging due to variable presentations
• CJD may initially present with psychiatric symptoms, leading to misdiagnosis
• Repeated neurological examinations and serial imaging may be necessary
• Biomarkers may be less sensitive in early disease stages or certain molecular subtypes 2, 1
• Special precautions are required for handling tissues and instruments due to prion resistance to standard sterilization 1