34c - Prions Flashcards
What are the progressive neurological disorders caused by infectious agents?
subacute sclerosing panecephalitis -measles
post-rubella panencephalitis
AIDS dementia complex
Progressive multifocal leukoencephalopathy - polyoma (JC)
Pathology of transmissible spongiform encephalopathies?
long incubate, rapid progression to fatal dementia.
Multifocal spongiform changes, astrogliosis, neuronal loss, amyloid plaques in some forms, minimal inflammation.
What chromosome is the prion protein exon encoded on?
Chromosome 20 in a single exon
What is PrPc?
the normal cell form of a prion protein
What is PrPsc?
pathogenic form of prion protein
WHat is PrPres?
pathogenic form of prion protein
What is scrapie?
a subacute, progressive ataxia of sheep. first found at 1 year of age in lymphatic tissues and itestines. By age 2 brain, followed by spongiform and disease.
What is Kuru?
first documented human TSE from Papua New Guinea and ritual cannibalism
What is CJD?
most common human TSE. clinical features of dementia, myoclonus, ataxia, and mutism near death. There are three forms.
What are the three forms of CJD?
sporadic (85%)
iatrogenic
familial
What is most common form of CJD?
sporadic (85%)
What is iatrogenic CJD?
transmitted from dural grafts, corneal grafts and hGH. Incubation of 1-2 years.
What is familial CJD?
15% of CJD, autosomal dominant pattern of transmission. Average age of onset is 45-50 years old. and Mean survival time from onset is 2 years.
How is CJD diagnosed?
Clincical course (rapidly progressive dimensia and myoclonus) Confirm by histology - cerebral spongiform changes, genreal lack of amyloid plaques.
Which type of CJD has specific EEG periodic complexes?
sporadic form.
What is GSS disease?
autosomal dominant mutation of 102 PrP that results in gait abnormalities and ataxia. Amyloid plaques+spongiform changes
Demntia less likely, average onset at 48 and death within 5 years.
What is FFI?
autosomal dominant muatation at 129 and 178 of PrP.
Onset of 49, 13 months till death.
Sleep disturbances and autonomic dysfunctino.
Histo = neuro loss, but rarely spongiform changes.
What is vCJD?
mad cow disease. Same as BSE.
Transmitted through contaminated beef and blood transfusion.
Onset at 29 years. 14 month survivial
Anxiety, depression, sensory abnormal, visual problems
Akinetic mutism at death.
All vicitms homozygous for methionine at position 129 of PrP
What genetic factor must patients have to be susceptible to vCJD?
homozygous for methionine at position 129 of PrP
What is EEG finding for vCJD?
atypical EEG without periodicity
How is vCJD diagnosed?
progressive neuropsych disorder of more than 6 months. Atypical EEG without periodicity
prion-positive tonsil biopsy
histo whos FLORID PLAQUES AND SPONGIFORM CHANGES IN BASAL GANGLIA
How can prions be killed?
saok instruments in 1 N sodium hydroxide for one hour then autoclave at 134C for one hour. Basically not fucking easy
What is structure of infectious forms of PrP?
high beta-sheet
Which TSE has peiordic complexes on EEG?
sporadic CJD
Which TSE has youngest age of onset?
vCJD at 29 yo.
Kuru is variable because you have to eat brain or some shit like that
Which TSE presents with personality and sensory changes?
vCJD
Which TSE presents with ataxia then dementia
kuru
GSS (dementia late)
Which Which TSE presents with dementia then myoclonus?
CJD
Which TSE presents with insomnia and autonomic dysfunction?
FFI
Which TSE has an autosomal dominant muatation at 129 and 178 of PrP.
FFI
Which TSE has an autosomal dominant mutation of 102 PrP
GSS
