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ZAHRAH MICRO > MI: Prion Disease > Flashcards

MI: Prion Disease Flashcards

1
Q

What is the rapid plasma reagent test?

A

Screening test for active syphilis

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2
Q

Name a CSF marker that supports the diagnosis of sCJD

A

14-3-3

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3
Q

What is a characteristic finding of CJD on a diffusion-weight MRI?

A

High signal in the caudate/putamen or at least in cortical regions (temporal, parietal, occipital)

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4
Q

What does ‘prion’ stand for?

A

Protein-only infectious agent

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5
Q

What are prion diseases and what do they cause?

A
  • Rare transmissible spongiform encephalopathies caused by prions
  • They lead to spongiform vacuolisation of the brain and rapid neurodegeneration
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6
Q

What is the prion protein gene and on which chromosome is it found?

A

PRNP gene, chromosome 20

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7
Q

What is a possible physiological role of the normal prion protein?

A

It may have some role in copper metabolism

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8
Q

Describe the structure of the normal prion protein.

A

Alpha-helix

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9
Q

Describe the structure of an abnormal prion protein.

A

Beta-pleated sheet

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10
Q

Why is the abnormal prion protein difficult to get rid of?

A

Resistant to proteases and radiation

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11
Q

How does prion replication take place?

A

Seeding of an abnormal prion protein (PrPsc) seems to act as a template which promotes the conversion of PrPc to the insoluble PrPsc

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12
Q

List some types of prion disease. Which type is most common?

A

Sporadic CJD (80%)

Acquired (<5%)

  • Kuru
  • Variant CJD (results from BSE epidemic)
  • Iatrogenic CJD

Genetic (15%)

  • PRNP mutations e.g. fatal familial insomnia, Gerstmann-Straussler-Sheinker syndrome
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13
Q

Give some examples of inherited prion diseases. What are they caused by?

A
  • Fatal familial insomnia
  • Gerstmann-Straussler-Sheinker syndrome

Caused by PRNP gene mutations

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14
Q

Describe the clinical features of sporadic CJD.

A

Rapid dementia with:

  • Myoclonus
  • Cerebellar dysfunction
  • Cortical blindness
  • Akinetic mutism
  • LMN signs

NOTE: usually in older people (>65)

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15
Q

What is the epidemiology and prognosis of sporadic CJD?

A
  • Mean age of onset 65 years (range 45-75 years)
  • Prognosis - death with 6 months
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16
Q

What are some possible causes of sporadic CJD?

A

No known cause

  • Somatic PRNP mutation
  • Spontaneous conversion of PrPc into PrPsc
  • Environmental exposure to prions
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17
Q

How might sCJD be diagnosed?

A
  • EEG - abnormal in 2/3
  • MRI
  • CSF
  • Neurogenetics
  • Brain biopsy
  • Autopsy - must be done by experience pathologist
18
Q

Describe the EEG appearance in sporadic CJD.

A

Triphasic complexes

19
Q

Describe the MRI appearance of sporadic CJD.

A

Increased intensity on DWI MRI of the basal ganglia and cortex

20
Q

Which markers will be raised in the CSF of a patient with CJD?

A

14-3-3

S100

21
Q

What is the only way of confirming a diagnosis of CJD?

A

Brain biopsy (usually at autopsy)

22
Q

Describe the histological appearance of CJD.

A

Spongiform vacuolisation

NOTE: there are amyloid plaques but these are different from the plaques seen in Alzheimer’s disease

23
Q

List the differential diagnosis for CJD.

A
  • Alzheimer’s disease
  • Vascular dementia
  • Mixed dementia (AD + vascular)
  • CNS neoplasms
  • Cerebral vasculitis
  • Paraneoplastic syndromes
  • Other CJD types (familial, variant)
24
Q

What is variant CJD?

A

CJD in younger people that has resulted from the BSE epidemic

25
Q

What animal disease is vCJD linked to?

A

Bovine spongiform encephalopathy (Mad cow disease)

26
Q

Describe the epidemiology and clinical features of vCJD

A
  • Younger age of onset - median age 26 years
  • Median survival 14 months
  • Psychiatric onset - dysphoria, anxiety, delusions, hallucinations
  • Followed by neurological symptoms - peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia
27
Q

What is a characteristic MRI feature of vCJD?

A

Pulvinar sign - bilateral hyperintensity in the posterior thalamus

Hockey stick sign

28
Q

How is the use of CSF markers different in vCJD?

A

14-3-3 and S100 are NOT useful in vCJD diagnosis

29
Q

Which investigation is most useful for vCJD?

A

Tonsillar biopsy

  • Prions localise in lymphoid tissue
  • Type 4t
  • 100% sensitive and specific
  • May be positive during incubation period before symptom onset

NOTE: this is not useful in sCJD

30
Q

Describe the role of neurogenetics in vCJD.

A

Almost 100% of patients are MM at codon 129 (in the PRNP gene)

31
Q

List some causes of iatrogenic CJD.

A
  • Human cadaveric growth hormone
  • Corneal transplants
  • Neurosurgical procedures e.g. dural grafts (pre-1991)
  • Blood transfusions
32
Q

Outline the clinical features of iatrogenic CJD.

A
  • Starts with progressive ataxia
  • Dementia and myoclonus occur at a later stage

Speed of symptom progession in iatrogenic CJD depends on route of innoculation (CNS innoculation is fastest)

33
Q

What is the inheritance pattern of inherited prion disease?

A

Autosomal dominant

34
Q

Which specific polymorphism in the PRNP gene is significant in inheried prion disease

A

MM (methionine-methionine) polymorphism at codon 129

(may confer earlier onset)

35
Q

What are some alternative diagnoses for someone presenting with features suggestive of prion disease?

A
  • Spinocerebellar ataxia
  • Huntington’s disease
36
Q

What is crucial to ask in the history when assessing inherited prion diseases?

A

Family history

37
Q

Describe the clinical features of Gerstmann-Straussler-Sheinker syndrome.

A
  • Slowly progressive ataxia
  • Diminished reflexes
  • Dementia

Onset age 30-70 years with 2-10 year mean survival

NOTE: PRNP P102L mutation is most common

38
Q

Describe the clinical features of fatal familial insomnia.

A
  • Untreatable insomnia / paranoia
  • Progressing to hallucinations and weight loss
  • Then a mute period
  • Dysautonomia (BP and HR dysregulation)
  • Ataxia
  • Late cognitive decline
  • (Thalamic degeneration)
  • Death 1-18/12 after start of symptoms

NOTE: PRNP D178N mutation is most common

39
Q

What is Kuru?

A
  • Prion diorder from Papua New Guinea that was spread due to the tradition of endo-cannibalism
  • Characterised by progessive cerebellar syndrome with late or absent dementia
  • Death occured within 2 years
40
Q

Outline the principles of treament of CJD.

A

Symptomatic

  • Clonazepam for clonus
  • (Valproate, levetiracetam, priacetam)

Delaying prion conversion

  • Quinacrine
  • Pentosan (intraventricular administration)
  • Tetracycline

Anti-prion antibody

  • Blocks peripheral prion replication and progession to disease in mice but cannot access CNS

Depletion of neuronal cellular prion protein

  • Prevents diease onset in mice and blocks neuronal cell loss and reverses early spongiosis
41
Q

Where should possible cases be reported to?

A
  • National prion clinic (Queen Square, UCL)
  • NCJDSU in Edinburgh

ZAHRAH MICRO (24 decks)

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