Demyelination and Dementia Pathology Flashcards

1
Q

What differenciates demyelinating disorders from neurological disorders which damage myelin and oligodendrocytes eg trauma?

A

there is preferential damage to myelin sheath

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2
Q

What can the diganosis of MS be supported by in terms of investigations?

A

slowed conduction in conduction studies and IgG oligoclonal bands in CSF

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3
Q

What part of the brain does MS principally affect?

A

white matter- this is where myelinated axons are

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4
Q

What are MS plaques?

A

well circumcribed and well demarcated irrregular shaped areas which have a glassly appearnace

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5
Q

Where are MS most commonly seen?

A

aroun small vessels -CNII; periventricular white matter; corpus callosum; brainstem and spinal cord

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6
Q

What is seen histologically in active plaques?

A

perivascular inflammatory cells; microglia (eating myelin) and ongiong demyelination

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7
Q

what is seen histologically in inactive plaques?

A

gliosis; little remaing myelinated axons and few oligodendroctes

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8
Q

What is dementia?

A

an acquired nad persistent generalised disturbance of higher mental functions in an otherwise fully alert person

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9
Q

How are neurodegenerative diseases characterised?

A

progressive loss of neurons typically affecting functionally related neuronal groups

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10
Q

What are the primary dementias?

A

alzhemiers; Lewy body; Pick’s (front-temporal); Huntingtons

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11
Q

What is seen macroscopically with Alzhemier’s?

A

cortical atrophy; widening of sulci and narrowing of gyri; hydocephalus ex vacuo

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12
Q

What areas of the brain are spared in alzhemiers?

A

occipital lobe; brainstem and cerebelilum

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13
Q

What is seen microscopically with alzhemiers?

A

extensive neuronal loss with astrocyte proliferation; neurofibrillary tangles; neuritic plaques; amyloid angiopathy

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14
Q

What are neurofibrillary tangles?

A

budnles of insoluble microtubules associated with tau protein in the cytoplasm of neurons

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15
Q

What are neuritic plaques?

A

focal, spherical collections of dilated , tortuous, neuritic process of neurones that surround a central smyloid core, often surrounded by peripheral reactive strocytes and microglia

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16
Q

What other name are neuritic plaques known by?

A

Abeta amyloid plaques;

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17
Q

Where are neurofibrillary tangles most commonly found?

A

hippocampus and temporal lobe

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18
Q

How is amyloid A-beta produced?

A

cleavage of amyloid precursor protein

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19
Q

What chromosome is amyloid precursor protein found on?

A

21

20
Q

What is the commonest familial cause of alzhemiers and how does it work?

A

apolipoprotein E e4 allele which dysregulates APP

21
Q

What chromosome is presenilin 1 found on?

A

chromosome 14

22
Q

What chromosome is presenilin 2?

A

chromosome 1

23
Q

What does abnormal production of A-beta amyloid result in?

A

A-beta oligomerisation which form amyloid fibrils and then plaques

24
Q

What do neuritic plaques lead to?

A

astrocyte and microgial activation–excitotoxicity

25
Q

What are the products of A-beta protein oligomerisation?

A

amyloid fibrils and A-beta oligomers

26
Q

What is the most toxic lesion that is produced from oligomerisation of A-beta protein?

A

A-beta oligomers

27
Q

What are the actions of A-beta oligomers?

A

enter synaptic space and cause excitotoxicity; tau hyperphosphrylation and mislocalisation- which also contributes to excitotoxicity

28
Q

What is amyloid angiopathy?

A

A-beta builds up in the wall of arterioles which stiffens and thickens the vessel walls and compromises the BBB

29
Q

What are the clinical differences between Alzhemiers and Lew body dementia?

A

Lewy body dementia has fluctuating cognitive dysfunction; frequent visual hallucinations and memory is affected later; has motor features of Parkinson’s

30
Q

What is seen macroscopically with Lew body dementia?

A

degeneration of the substancia nigra

31
Q

What is seen microscopically with Lew-body dementia?

A

loss of prigmented neurons; reactive gliosis and microglial accumulation with remaining neurones having Lewy bodies

32
Q

What is a Lewy body?

A

discrete eosinophilic cytoplasmic inclusion consisting of a dense core, surrounded by fibrils of alpha-synuclein

33
Q

How many CAG repeats are needed for Huntington’s disease to occur?

A

> 35 repeats

34
Q

What is seen macroscopically with Huntington’s disease?

A

atrophy of caudate nucleus>putamen>globus pallidus with hydrocephalus ex vacuo; later cortical atrophy

35
Q

What does atrophy of the caudate nucleus lead to?

A

loss of inhibitory regulation of motor activity

36
Q

What does later cortical atrophy correspond to?

A

onset of dementia

37
Q

What are the symptoms of Pick’s disease?

A

personality and behavioural change; speech and comm problems; changes in eating habits and reduced attention span

38
Q

When is the typical onset of Pick’s disease?

A

between 50 and 60 years

39
Q

Why is there personality changes in Pick’s disease?

A

frontal lobe atrophy

40
Q

Why is there language issues with Pick’s disease?

A

temporal lobe atrophy

41
Q

What is seen macroscopically with Pick’s disease?

A

extreme strophy of the frontal and temporal lobes

42
Q

What are the histological hallmakrs of Pick’s disease?

A

Pick’s cells (swollen neurons) and Pick’s bodies ( intracytoplasmic filamenouts inclusions)

43
Q

What type of protein is found in Pick bodies?

A

protein Tau

44
Q

What is multi-infarct dementia?

A

deterioration of mental functioning due to cumulative damage to the brain through hypoxia as a reult of multiple blood clots within the blodd vessels supplying the brain

45
Q

Is vascular dementia more common in males or females?

A

men

46
Q

What is the defining clinical feature of vascular dementia?

A

patients are aware of their mental decifits which provokes depression and anxiety

47
Q

What are hte differenes between Alzhemiers and vascular dementia?

A

vascular dementia has abrupt onset and a stepwise progression; patient will have a hx of HT or stroke which will be seen on CT or MRI