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Neurology Micro > Prions > Flashcards

Prions Flashcards

1
Q

What agent is responsible for transmissible spongiform encephalopathies (TSE)?

A

Prions

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2
Q

What pathology’s are associated with TSE?

A

Multifocal spongiform changes, Astrogliosis, Neuronal loss, Amyloid plaques in some forms and
Minimal inflammatory response

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3
Q

TSE is typically characterized by

A

Long incubation period, but then rapidly progressive. Invariably fatal dementia

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4
Q

What is the prion theory?

A

TSE agents are extremely resistant to treatments that damage nucleic acids and viruses. TSE agents are now believed to be proteinaceous infectious particles, “prions”

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5
Q

What are the four characteristics of prion proteins?

A
  1. Highly conserved among humans and various animals
  2. Encoded in a single exon on human chromosome 20
  3. Highly expressed in neurons and lymphocytes
  4. Final product is a 209 amino acid glycoprotein that is anchored to cell surfaces by a fatty acid
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6
Q

What are the two forms of prions?

A

Normal is PrPc and Pathogenic form is PrPsc or PrPes

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7
Q

Can PrPc and PrPsc have identical sequence?

A

Yes but they can fold differently

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8
Q

What are the characteristics of PrPsc’s altered folding?

A

Unusually stable, only partially degraded by proteases
Aggregates in the cytoplasm of cells
Leads to apoptosis of neurons, but disease mechanism is not understood

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9
Q

Must PrPc be expressed to contract disease?

A

You betcha

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10
Q

What’s scrapie?

A

A subacute, progressive ataxia of sheep
First found at one year of age in lymphatic tissues and intestines
By two years of age, brain is infected, followed by spongiform changes and clinical disease
Not understood how PrPsc reaches CNS, but follicular dendritic cells may be intermediary

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11
Q

What’s KURU?

A

First documented human TSE. Transmitted by ritual cannibalism. No cases since cannibalism stopped

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12
Q

What’s the most common human TSE?

A

CJD. It’s extremely rare

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13
Q

What are the clinical features of CJD?

A

Dementia, Myoclonus, Ataxia, and Mutism near death

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14
Q

What are the characteristics of sporadic CJD?

A 
85% of all CJD
Average age of onset is 60 years
Mean survival time is 5-8 months
No risk factors have been identified
Exact cause unknown, possibly a chance conversion of PrPC to PrPSc?
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15
Q

What sources have been documented as transmitting iatrogenic CJD?

A

Dural grafts, corneal grafts, and human growth hormone. No convincing evidence of blood transmission

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16
Q

Does iatrogenic or sporadic CJD have a shorter incubation period?

A

Shorter incubation period (1-2 years) for dural and corneal grafts than for sporadic CJD

17
Q

What are the characteristics of familial CJD?

A 
15% of total CJD
Autosomal dominant pattern
Associated with specific alterations in PrP
Average age of onset is 45-50 years old
Mean survival time is 2-4 years
18
Q

What Sx suggest CJD?

A

Rapidly progressive dementia and Myoclonus

19
Q

How do you confirm CJD?

A

Confirm by histology: cerebral spongiform changes
and general lack of amyloid plaques. Check CSF to rule out tertiary syphilis or SSPE
(Specific to the sporadic form: Characteristic periodic complexes in EEG)

20
Q

What are the characteristics of GSS dz?

A

Autosomal dominance pattern

Most often associated with a mutation at codon 102 of PrP

21
Q

What are the clinical feature of GSS?

A 
Clinical features are variable, differ from CJD
Average age onset is 48
Mean time to death is 5 years or more
Gait abnormalities and ataxia
Dementia is less common, may occur late
22
Q

Diagnostic features of GSS?

A

No characteristic EEG

Amyloid plaques in addition to spongiform changes

23
Q

What are the characteristics of FFI?

A

Autosomal dominant pattern

Mutations at codons 129 and 178 of PrP

24
Q

What are the clinical features of FFI?

A

Average age onset is 49, 13 months to death
Clinical features
Sleep disturbances
Autonomic dysfunction

25
Q

What histologic features do you see with FFI?

A

Histopathology reveals much neuronal loss, but rarely spongiform changes

26
Q

What’s variant CJD?

A

First reported in UK in the 90s. Patterns of the protease-resistant form of PrP confirmed vCJD is the same as BSE

27
Q

How does transmission of vCJD occur?

A

Through ingestion of contaminated beef and blood transfusions

28
Q

What are infectious sources of vCJD?

A

Brain, spinal cord, retina, DRG, bone marrow, tonsils, spleen, lymph nodes, appendix and blood

29
Q

What are the clinical features of vCJD?

A

Average age onset is 29 years with 14 month mean survival time. Sx= anxiety, depression and sensory abnormalities. Visual problems late and akinetic mutism at death

30
Q

Have all victims of vCJD been homozygous for methionine at position 129 of PrP?

A

Yes

31
Q

Dx of CJD?

A

Progressive neuropsychiatric disorder of more than 6 months. Atypical EEG without periodicity. Prion-positive tonsil biopsy. Histology reveals florid plaques and spongiform changes in basal ganglia

32
Q

What can you do to prevent TSE?

A
  1. Genetic counseling for familial forms
  2. Ruminant feed ban, import ban
  3. Cull sick animals, screen brain tissue with ELISAs
  4. Avoid pooled sources of grafts and properly sterilize equipment
  5. Soak instruments in 1 N sodium hydroxide for one hour followed by autoclaving at 134 C for one hour
  6. Restrict blood donations
33
Q

Can a single PrP of specific amino acid sequence assume more than one conformation?

A

Yes.

34
Q

One conformation (PrPc) is greatly favored in an uninfected. Do spontaneously pathogenic forms commonly occur?

A

No: a spontaneous pathogenic form is very rare, hence late onset of sporadic CJD

35
Q

True or false, most PrP “strains” differ by minor amino acid substitutions which dictate final conformation?

A

True

36
Q

True or false, a “template” PrP propagates the final conformation?

A

True

37
Q

Is there believed to be a species barrier with prions?

A

Yep

Neurology Micro (6 decks)

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