Lecture 59 Prions, Demyelinating, HIV dementia

Question 1

What is a TSE?

Answer 1

Transmissible Spongiform Encephalopathy

Question 2

What do prion diseases do to the brain?

Answer 2

Cause spongiform development (brain gets holes in it and looks like a sponge)

Question 3

Name the four known human prion diseases

Answer 3

1) Kuru
2) Creutzfeldt-Jakob Disease (CJD)
3) Gertsmann-Straussler-Scheinker
4) Fatal Familial Insomnia

Question 4

Kuru

Answer 4

Mostly in a tribe in Papua New Guinea
Spread by ritual practices of eating relatives
Caused neuronal loss in the brain leading to ataxia, choreiform movements, and dementia
Tremors common that progress to motor function loss and paralysis

Question 5

CJD

Answer 5

Resembles Kuru–ataxia, seizures
Onset to death 15-20 months
Mostly disease of the elderly 60-70 years
New variant showing up in youth assoc with BSE (mad cow disease)
Infection from neurosurgery, pituitary hormone, corneal transplants, and BSE

Question 6

What are prions?

Answer 6

Infectious proteins

Do not contain any DNA/RNA

Question 7

Prions are very resistant to inactivation, what would disable them?

Answer 7

Extended autoclaving
5% sodium hypochlorite
1 N NaOH

Question 8

Prion propagation

Answer 8

One bad protein causes a conformational change to others

one bad apple spoils the barrel

Question 9

Describe the conformational change that takes place in PrPc

Answer 9

This is a normal protein that is produced and degraded
Conformational change is from alpha-helices to beta-sheets which impairs the breakdown of the protein and it accumulates in the brain

Question 10

Prion manifestations

Answer 10

Spongiform lesions in the brain
Amyloid plaque formation in some cases
No immune response

Question 11

Prion diagnosis

Answer 11

No clear way to diagnose
Suspect in anyone with progressive subacute or chronic mental deterioration or loss of muscle function
Generally 40-70 years old
Genetic screens can help identify inheritable forms of the disease, but are not useful in sporadic causes

Question 12

Prion treatment

Answer 12

Invariably fatal within a short period of time after diagnosis

Question 13

Prion epidemiology/causes

Answer 13

1) Inherited form: point mutations in genome predispose to PrPc conversion
2) Sporadic form: Most cases of disease, no mutation in PrP gene, either horizontal transmission from an animal or spontaneous conversion of protein
3) Infectious form: direct inoculation from a medical procedure such as corneal transplant, neurosurgery, pituitary hormones, dura mater grafts

Question 14

How is new variant CJD different?

Answer 14

Happens in younger patients
Has amyloid-like plaques and intense halo of spongiform degeneration
Most likely caused by BSE spread from cattle to humans through consumption

Question 15

Are prions transmissible by blood?

Answer 15

Yes

Can’t give blood if spent time in great britain

Question 16

Prion prevention

Answer 16

Don’t eat CNS from cattle over 6 months

Question 17

What can happen 2-10 years after being infected with measles?

Answer 17

SSPE = Subacute Sclerosing Panencephalitis

Rare, intracellular inclusions in neuronal cells

Question 18

PML features

Answer 18

Progressive Multifocal Leukoencephalopathy
Assoc. with underlying immune deficiency, allows latent JC virus to manifest
JCV attacks oligodendrocytes => tissue destruction
More common in AIDS patients

Question 19

Multiple sclerosis

Answer 19

Demyelinating disease, onset in early adulthood
Patchy lesions in white matter
Relapsing or intermittent
Possible viral cause?

Question 20

HIV and CNS

Answer 20

HIV is very commonly found in the CNS of AIDS patients
Causes cognitive impairments, motor problems, social withdrawal
Similar to Alzheimer’s disease progression
HIV doesn’t directly infect or damage neuronal cells, damage to these cells is secondary