Prion disease Flashcards by Helen Max

What is a prion?

An infectious agent consisting only of protein, which can fold in multiple, structurally distinct ways, at least one of which is transmissible to other prion proteins, leading to disease that is similar to viral infection.

How well did you know this?

Not at all

Perfectly

Which diseases are thought to be caused by prions?

The rare Transmissible Spongiform Encephalopathies (TES)

How well did you know this?

Not at all

Perfectly

Which system is affected by all known prion diseases in mammals?

The nervous system: all affect the structure of the brain or other neural tissue, resulting in rapid neuro-degeneration. All are currently untreatable and universally fatal.

How well did you know this?

Not at all

Perfectly

What is PrP?

Prion protein - the protein that prions are made of, which may occur in both infectious and non-infectious forms. Healthy form found throughout the body, even in healthy people and animals.PrP found in infectious material has a different structure and is resistant to proteases

How well did you know this?

Not at all

Perfectly

What is PrP^C?

PrPC is a normal protein found on the membranes of cells. The C refers to ‘cellular’ PrP. Predominantly expressed in CNS

How well did you know this?

Not at all

Perfectly

Which chromosome has the gene for PrPC?

How well did you know this?

Not at all

Perfectly

What is PrP^SC?

The infectious isoform of PrP. Sc refers to ‘scrapie’, the prototypic prion disease, occurring in sheep.

Able to convert normal PrPC proteins into the infectious isoform by changing their conformation, or shape; this, in turn, alters the way the proteins interconnect. PrPSc always causes prion disease. PrPSc has a higher proportion of β-sheet structure in place of the normal α-helix structure.

Protease/radiation resistant.
Seed of PrPSc acts as template which promotes irreversible conversion of PrP to insoluble PrPSc

How well did you know this?

Not at all

Perfectly

Is there currently a cure for prion disease?

Nope

How well did you know this?

Not at all

Perfectly

Which 2 genetic mutations are associated with prion disease?

Codon 129 polymorphism

Specific PRNP mutations

How well did you know this?

Not at all

Perfectly

Give 2 neuro-genetic differential conditions to consider

Huntington’s

Spinocerebellar ataxia

How well did you know this?

Not at all

Perfectly

What treatment may be given for the symptomatic relief of myoclonus in CJD?

Clonazepam
Sodium valporate
Levetiracetam
Piracetam

How well did you know this?

Not at all

Perfectly

What is myoclonus?

Irregular short duration jerk like episodes involving the somatic (skeletal) musculature

How well did you know this?

Not at all

Perfectly

In CJD which treatments are used to delay prion “conversion”?

Quinacrine
Pentosan
Tetracycline

How well did you know this?

Not at all

Perfectly

What are the 3 broad types of prion disease and what percentage does each make up?

Sporadic CJD (sCJD) - 80%
Acquired CJD -

How well did you know this?

Not at all

Perfectly

Which 3 prion diseases belong to the “acquired CJD” category?

vCJD (variant)
Iatrogenic
Kuru

How well did you know this?

Not at all

Perfectly

List 4 inherited prion diseases/types of disease

Familial CJD
Gerstmann-Straussler-Scheinker syndrome (GSS)
Fatal familial insomnia (FFI)
Various atypical dementias

How well did you know this?

Not at all

Perfectly

What are the EEG changes in sCJD?

Serial EEG shows periodic triphasic changes

How well did you know this?

Not at all

Perfectly

What are the EEG changes in vCJD?

Non-specific slow waves

How well did you know this?

Not at all

Perfectly

What are the MRI changes in sCJD?

Normal/highlighting basal ganglia

How well did you know this?

Not at all

Perfectly

What are the MRI changes in vCJD?

Posterior thalamus highlighted on MRI-T” (pulvinar sign)

How well did you know this?

Not at all

Perfectly

What are the MRI changes in inherited prion disease?

Sometimes high signal in basal ganglia

How well did you know this?

Not at all

Perfectly

Which two types of prion disease give a high basal ganglia signal on MRI?

sCJD and inherited prion diseases

How well did you know this?

Not at all

Perfectly

Which protein may show an elevated CSF level in prion disease?

14-3-3 protein

How well did you know this?

Not at all

Perfectly

Which type of prion disease is most associated with an elevated 14-3-3 protein?

Study These Flashcards

sCJD

Is CSF 14-3-3 a good diagnostic test for CJD?

No, it's not sensitive or specific Only half of patients diagnosed with CJD have an elevated 14-3-3 protein. About 1/3 of patients who do have an elevated 14-3-3 protein are found to have a different neurological disease, not CJD

What does CJD stand for?

Creutzfeldt-Jakob disease

In which type of CJD are diagnostic *mutations* present on PNRP (prion-protein gene) analysis?

Inherited prion diseases (PNRP mutations not usually seen in sporadic or acquired CJD, but certain polymorphisms are associated with increased susceptibility)

Which PNRP (prion-protein gene) polymorphism is a recognised genetic marker for increased CJD susceptibility in Caucasions?

Codon 129 - homozygosity (MM or VV) associated with increased risk

In which type of CJD are *all* cases homozygous MM at codon 129?

vCJD in sCJD and iatrogenic cases, most are homozygous

Which type of homozygosity is most commonly associated with CJD susceptibility, MM or VV?

MM But VV also has higher susceptibility than heterozygous state.

In sCJD and iatrogenic CJD, which types of PrP^SC are detected by Western blot?

Types 1-3

In vCJD, which type of PrP^Sc protein is detected by Western Blot and from where is the sample taken?

Type 4t From tonsillar biopsy (100% sensitivity and specificity)

Give 2 post-mortem findings in sCJD

Spongiform vacuolation | PrP amyloid plaques

Give 2 post-mortem findings in vCJD

PrP^Sc detectable in CNS and lymphoreticular tissue | Florid plaques

Describe the aetiology of sCJD

Somatic (ie not inherited) PRNP mutation OR Spontaneous conversion of PrP^c to Prp^Sc and subsequent seeding

Describe the aetiology of vCJD

Exposure to bovine spongiform encephalopathy (BSE, "mad cow disease")

Describe the aetiology of iatrogenic CJD

Innoculation with human prions - commonly during surgery

Describe the aetiology of kuru

Exposure to human prions through cannibalism | Papua New Guinea

What is the inheritance type (ie dominant/recessive etc) of the inherited prion diseases Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia?

Autosomal dominant

How many families in the world have fatal familial insomnia (FFI)?

40-50, with ~100 affected individuals

List 5 clinical features of sCJD

``` Rapid, progressive dementia Myoclonus Cortical blindness Akinetic mutism Lower motor neuron signs ```

What is the mean age of onset of sCJD?

45-75 years

What is the mean survival time of sCJD?

6-12 months of symptom onset

How does the age of onset differ in vCJD (compared to sCJD)?

Younger - typically around 30 years

What is the mean survival time of vCJD?

~14 months

Which symptoms develop first in vCJD?

Psychiatric: anxiety, paranoia, hallucinations

In vCJD, which group of symptoms follow the psychiatric symptoms?

Neurological: peripheral sensory symptoms, ataxia, myoclonus

List 3 late stage symptoms of vCJD

Chorea Ataxia Dementia

What determines the speed of progression of iatrogenic CJD?

Route of inoculation - fastest if introduced directly into CNS

What is the first symptom of iatrogenic CJD?

Progressive ataxia

Give 2 later stage symptoms of iatrogenic CJD

Dementia | Myoclonus

How long is the incubation period of kuru?

~45 years

How does kuru present and what is the survival time from presentation?

``` Progressive cerebellar syndrome 3 stages: ambulant, sedentary, terminal "Laughing sickness" - pathologic bursts of laughter Late/absent dementia Death within 2 years ```

When was the kuru epidemic in PNG?

1950s/60s

When does Gerstmann-Straussler-Scheinker (GSS) present and what is the mean survival from this point?

Develops between 20-60 years | ~5 year survival

What are the 2 stages of GSS?

Dysarthria Cerebellar ataxia Dementia (Gradual progression)

How does fatal familial insomnia (FFI) initially present?

Insomnia and paranoia

How do the symptoms of FFI progress?

Hallucinations and weight loss, followed by a final mute period

What is the mean survival time of FFI?

1-18 months after start of symptoms

Prion disease Flashcards

(59 cards)