Creutzfeldt-Jakob disease

From Ganfyd

Introduction

Creutzfeldt-Jakob disease (CJD) is a rare, progressive, incurable degenerative neurological condition. The mode of acquiring the disease is variable: sporadic, inherited, familial, iatrogenic and possibly via ingestion of beef from cattle with bovine spongiform encephalopathy. As such, it is transmissable, but is not infectious in the conventional microbiological sense. The putative causative agent is an abnormal folded protein called prion protein. (PrP). The human prion diseases are more correctly classified as transmissible spongiform encephalopathies(TSE)and this term is now preferred by workers in the field. The main types of TSE are detailed here for convenience as many use the clinical term CJD rather than TSE:

• Creutzfeldt-Jakob disease (CJD)
  • At least 5 variants
• new variant Creutzfeldt-Jakob disease(nvCJD)
• Kuru
• Genetic Creutzfeldt-Jakob disease (gCJD)
  • Autosomal dominant CJD
  • Genetic TSE patients with insert mutation in the PRNP
• Gerstmann-Staussler-Scheiner disease(GSS)
• Fatal familial insomnia (FFI)
• Prion protein cerebral amyloid angiopathy (PrP-CAA).

Aetiology

Clinical

Incidence

• 1-2 per million
• All forms have a genetic association
  • In western populations 79% have methionine-methionine genotype at PrP₁₂₉ compared to 39% in reference population.

Disease Characteristics

• Peak onset 60-64 years
• Mean duration 8.5 months
  • range 2 months to 10 years(Definite French case ten years plus, cases of incidential prion protein change at neuro-postmortem have been discovered in UK-personal knowledge)
  • 90% dead in less than 1 year, 70% in less than 6 months from first presentation

Clinical Presentation

Prodrome

Present in 39%

• asthesia (23%)
• depression
• weight loss...no anorexia (15%)
• sleep disorder

Onset

• Gradual in 81%
• Rapid 19% (Can present as a febrile leukoencephalopathy rarely-more common in Asia)
• At first medical presentation, 10% have single symptom or sign, 46% psychiatric symptoms, 40% have neurological signs and 14% mixed picture.
• Dementia 29%
• Changes in behaviour 30%
• Cortical dysfunction 18%
• Cerebellar 29%
• Visual symptoms 17%
• Vertigo 8%
• Dysphasia
• Headache 10%
• Movement disorder 1%

Progress

• Dementia in 94%
• Behaviour issues in 45%
• Cortical dysfunction in 39%
• Movement disorder in 90%
  • Myoclonus 84%
  • Extrapyramidal 60%
• Cerebellar 56%
• Pyramidal 44%
• Visual 40%
• Headache 15%
• Lower Motor Neuron signs 12%
• Vertigo 11%
• Seizures 9%
• Sensory signs 7%
• Cranial nerve signs 2%

Neuropathology

• Spongioform degeneration CNS
• Abnormal insoluble protein deposits in CNS this is termed PrP^Sc. The normal soluble form is called PrP^C

Investigations

Blood tests

• None useful

Radiology

• MRI, in particular cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging in sCJD and other features in nvCJD.

CSF

• CSF 14-3-3 has a high sensitivity (80-90%) and lower specificity (<90%). It can be raised in anti-NMDAR limbic encephalitis which should be considered in differential
• CSF S-100b if raised has over 90% specificity
• p-tau/t-tau ratio is low cf Alzheimer's disease (ie t-tau raised)

Other

• serial EEG
  • useful in classic CJD, said to be abnormal in 77% if repeated often enough and characteristic in 40%
  • not useful in nvCJD
• MRI - nvCJD has characteristic changes
• Biopsy - 20% short term mortality !

Treatment

Medical

Surgical

Prevention

Post exposure prophylaxis

Notification

Not one of the statutorily notifiable diseases; but systems are in place for the surveillance of CJD and vCJD. Lookback exercises may be required if other individuals may be at risk from exposure to tissue from a patient.

ICD code

External links

• Main HPA CJD page
• Guidance on local reporting of creutzfeldt jakob disease (cjd) and local action by consultants in communicable disease control (CsCDC)
• "Transmissible spongiform encephalopathy agents: safe working and the prevention of infection: Guidance from the Advisory Committee on Dangerous Pathogens and the Spongiform Encephalopathy Advisory Committee"

References