Creutzfeldt-Jakob disease

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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).

Contents

Classification

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:

Aetiology

Prion protein with transmissable conformational change.

Clinical

Incidence

Annual number of deaths since 1990 in UK
  • 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%

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%
  • 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 PrPSc. The normal soluble form is called PrPC

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
    • Diffusion MRI (T2-weighted and FLAIR showing restricted diffusion confined to the gray matter in the cortical ribbon sign is diagnostic of CJD in a rapidly progressive dementia
  • MRI - nvCJD has characteristic changes

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%
    • Generalised, periodic, biphasic or triphasic sharp-wave complexes at 1-2Hz
    • Not useful in nvCJD
  • Biopsy - 20% short term mortality !
    • Not usually done

Genetic studies

  • Methionine-valine (M-V) polymorhism at prion protein codon 129 combined with type of prion protein analysis:
    • MM1/MV1
      • Early visual symptoms
    • MV2
      • Ataxia tends to be early
    • VV2
      • Ataxia tends to be early
    • MM2-cortical
      • Tends to be older patients with prolonged course
      • Rarer
    • MM2-thalamic
      • Psychiatric or insomina presentations commoner
    • VV1

Treatment

Medical

  • Supportive care
  • Marked deterioration with anti-psychotics has been seen

Prevention

  • There are important infection control measures. Prion protein must not be allowed to contaminate surgical instruments used in others or affected patients used for tissue donation.
  • Infectivity by ingestion is low

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.

External links

References

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