8.3.2 CNS Tumours Flashcards

Question

What are prion diseases?

Answer 1

Abnormal cellular protein accumulations which lead to cell injury in and out of the cell: - Neurone cell death - Synapse loss - Microvacuolations - Lack of inflammation

Answer 2

Causes abnormal protein aggregates to accumulate in local cells

Answer 3

Sporadic Familial Iatrogenic Ingested (think of House episode with the water)

Answer 4

* Creutzfeldt- Jakob Disease and variant CJD * Scrapies (sheep) * Bovine spongiform encephalopathy (Mad Cow disease)

Answer 5

Normal brain proteins are rich in alpha helices **Initiation** Prion disease ingested. inoculated or sporadic, this causes conformational change to beta pleated sheet **Propagation** Abnormal proteins cause surrounding proteins to undergo conformational change from alpha helices to beta pleated sheets **Aggregation** Abnormal proteins aggregate forming amyloid plaques and spongiform brain

Answer 6

* Normally sporadic (familial form) * 1 per million very rare * Rapidly progressive dementing illness * Subtle changes in memory * Cerebellar ataxia * Global dementia * Definitive diagnosis- post mortem * Often brain looks normal, may have atrophy or ventricular enlargement

Answer 7

* Affects young adults * Slower progression * Starts with behavioural issues * Exposure due to cattle- e.g. meat and blood transfusions * Prolonged incubation, 15 years

Answer 8

Loss of neurones Accumulation of protein aggregates

Answer 9

Changes in: - Cognitive - Memory - Behaviour - Language

Answer 10

Movement disorders, hypo/hyperkinetic

Answer 11

Ataxias, motor neurones can also be hit

Answer 12

3% of 65-74 year olds, increases with age Sporadic 90% of the time Can be familial which causes earlier onset, 5-10%

Answer 13

Alpha beta plaques and neurofibrillary tangles (tau) form This accumulation causes neuronal damage, this leads to loss of neurones Loss of neurones causes cortical atrophy and shrunken brain Affects frontal, temporal and parietal lobes

Answer 14

**Amyloidogenic pathway** - Transmembrane protein on chromosome 21 cleaved to alpha beta monomer by beta and and gamma secretase - Alpha beta monomers clump together forming oligomers, these then aggregate forming fibrils which then form tangles - Tau aggregates are formed by alpha beta oligomers becoming hyperphosphorylated, this causes neuronal damage **Non-amyloidogenic pathway** - Alpha and gamma secretase cleave

Answer 15

Protein which causes Alzheimer's is found on chromosome 21 In Down syndrome, there are 3 chromosome 21s, therefore more likely to have plaque and tangle formation

Answer 16

Impaired memory Impaired intellectual function Altered mood and behaviour Disorientated

Answer 17

Loss of dopaminergic neurones in the substantia nigra pars compacta Lewy body involvement (alpha synuclein)

Answer 18

**S**ometimes **TRAPPED** **D***ck **M**eans **F**emoral **H**ernia **S**huffling gait **T**remor **R**igidity **A**kinesia **P**ill-rolling tremor **P**ostural instability **E**xpressive aphasia **D**ementia **D**epression **M**icrographia **F**acial weakness **H**ypokinesia

Answer 19

Autosomal dominant condition Increased CAG repeats Mutant protein broken down to aggregates which causes damage Loss of inhibitory neuronal projection to corpus striatum

Answer 20

**CDCD** **C**horea **D**istonia **C**o-ordination loss **D**ecline in cognition