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Flashcards in Neurodegenerative Disorders Deck (63):
0

What are the main indications of neurodegenerative disorders ?

Loss of neurons in brain and spinal cord
Progressive symptoms
Irreversible symptoms

1

Give examples of neurodegenerative disorders

Alzheimer's
Parkinson's
Huntington's
Frontal temporal dementia/picks
CBGD
Motor neuron disease
PSP - progressive supra palsy

2

What is the most common neurodegenerative disorder ?

Alzheimer's

3

Define dementia:

An acquired, persistent intellectual impairment involving at least 3 of these domains:
- language
- visuospatial skills
- emotion/personality
- memory
- cognitive/executive function s

It is a failure of higher brain functions

4

Why are the pathological markers of AD?

Cortical extracellular senile plaques and neurofibrillary tangles

5

What are the pathological markers of PD?

Lewy bodies- intracellular

6

What are the pathological markers of PSP?

Subcortical neurofibrillary tangles

7

What are the pathological markers of CBGD?

Cortical and subcortical achromatic inclusion bodies

8

What are the pathological markers of Huntingtons disease ?

Selective loss or neurons and gliosis

9

What are the pathological markers of picks disease ?

Selective temporal lobe atrophy and picks bodies

10

What was PD first described as ?

Shaking palsy in 1817

11

What does PD cause ?

A kinetic rigid syndrome
- loss of movement
- increased muscle tone

12

Do patients normally die form PD and what are their life expectancies ?

No they normally die of a complication of the disease such as bronchopneumonia or bed sores

10-15 years but some people survive decades - the drug treat,net significantly prolongs life

13

What are the main symptoms of Parkinson disease ?

Tremor
Rigidity
Speech difficulty
Postural changes
Akinesia

14

What do Parkinson's patients do to try and help initiate movements ?

Use visual cues such as a time on a clock

15

What are the pathological effects of Parkinson's disease ?

Loss of neurons in substantia nigra
Lewy bodies - spherical eosinophilic inclusion bodies
It is the dopaminergic neurones that are affected
Loss of the excitatory and inhibitory nigro-striatal pathways
Affects midbrain nuclei

16

What are the causes of Parkinson's disease ?

Unknown - idiopathic

17

What things have caused associated disorders of Parkinson's disease ?

Drug induced - iatrogenic- dopamine antagonist
MPTP induced - contaminated amphetamines which kills off dopamine neurons in substantia nigra causing rapid onset of Parkinson's disease
Post encephalitic- viral illness that triggers degeneration of nerve cells in substantia nigra

18

What happens to the pathways in Parkinson's disease ?

Lose indirect and direct pathways so it reduces thalamic output causing a reduction in motor output

19

Describe huntingtons disease

Gradual onset
Normal onset is 30-50 years - younger means it's more sever
Progressive
Inherited
Death within 10-20 years
Main symptoms are chores and dementia

20

What are the symptoms that lead to dementia in huntingtons disease ?

Irritability
Moodiness
Antisocial behaviour- aggressive, angry and unpleasant

21

What are th symptoms that lead to gross chore inform movements of huntingtons disease ?

Fidgeting
Restlessness

Gross choreiform movements cause over reaching and grasping things too tightly

22

Where are neurons lost in huntingtons disease?

Cerebral cortex
Corpus striatum

23

Which neurons are the first to be affected in huntingtons disease ?

Medium sized spiny neurons containing GABA and enkephalins

24

What happens to neurotransmitters in huntingtons disease ?

Decrease in GABA and its enzyme GAD
Decrease in ACh and its enzyme choline acetyl transferase
Either no change to dopamine or a slight increase

25

What happens to the pathway in huntingtons disease ?

Lose some of the negative feedback control on dopamine causing increased dopamine output

26

What are the causes of huntingtons disease?

Autosomal dominant disorder
Affects shorts arm of chromosome 4
Locus 4p16.3 codes for protein Huntingtin - gives rise to poly glutamine repeat - CAG
More than 36 repeats means you have the disease

27

Describe progressive supranuclear palsy

Idiopathic
Death within 2-12 years
Affects subcortical grey matter- loss of neurons
2x more prevalent in men
Causes aspiration and inanition
Starts 45-75 years

28

What are the main symptoms of PSP?

Progressive dementia causing exaggerated emotional response
Motor disorders
- opthalmoplegia, pseudobulbar palsy and balance/posture impaired
Sometimes causes limb rigidity, bradykinesia and hyperreflexia

29

What is opthalmoplegia ?

Loss of eye movements
First the vertical gaze and then horizontal

30

What balance/postural impairments occur in PSP?

Unexplained falls
Neck extended and rigid to flexion so it's difficult to move

31

What are he pseudobulbar palsy symptoms of PSP?

Facial weakness
Dysarthria
Dysphagia
Exaggerated gag reflex

32

What are the pathologies of PSP?

Neurodegeneration
Neurofibrillary tangles in midbrain, pons, basal ganglia, dentate nuclei of cerebellum - in all motor control areas
Decrease in da in cerebellum and caudate nucleus

33

What are neurofibrillary tangles ?

Aggregates of tau protein in micro tubules

34

Describe cortical basal ganglionic degeneration

Rare
Non inherited
Onset is Middle age/elderly

35

What are the symptoms of CBGD??

Bradykinesia/rigidity
Clumsiness
Speech- apraxia, asphasia and dysarthria
Myoclonus
Postural instability

36

What is dysarthia?

Inability to vocalise

37

What are the pathologies of CBGD ?

Atrophy of frontal and parietal cortex
Cell loss and gliosis in cortex, thalamus, red nucleus, lentiform nucleus, substantia nigra and locus coerulus

38

What are the different disorders in motor neurons disease ?

Amyotrophic lateral sclerosis - ALS- loss of both upper and lower
Primary lateral sclerosis - PLS - loss of upper
Progressive muscular atrophy - PMA - loss of lower
Pseudobulbar palsy -PBP- loss of lower
Preogressive bulbar palsy -PrBP- loss of upper

39

Describe ALS

Begins 30-60 years old
Degen of both upper and lower( anterior horn cells)
Muscle denervation
90-95% sporadic and 5-10% familial
Fatal in 3-5 years

40

What are the symptoms on motor neurons disease ?

Bulbar 20% - chewing, swallowing, breathing and speaking
Upper extremities and lower extremities 40%
Muscle wasting and weakness
Affected muscles are easily tired, stiff and twitch

41

What is ALS-PDC?

Occured in chaumoro people of Guam
They ate flying foxes which act cycads that contain toxic amino acid beta-methylamino l-Alanine

42

What is picks disease ?

It's the most common frontotemporal dementia - 20-25%
Onset 56-58 years
Duration 8-11 years
No known genetic factor but 45% have first degree relatives with the disorder

43

What are the symptoms of picks disease ?

Personality changes - inappropriate social behaviours, impulsive, neglect of hygiene
Emotional changes- apathy, depression, mania, anger and irritability
Speech- no fluency, echolalia, dysarthia, palilalia
Fm develop voracious appetites

44

What are the pathologies of picks disease ?

Neuronal cell loss causing astrogliosis
Swollen ballooned neurons - picks cells

45

What is the cause of picks disease ?

Unknown
- decrease in serotonin receptors and serotonin
Decrease in somatostatin in brain and CSF

46

Describe Alzheimer's disease

Most common form of dementia
Sporadic - 90%
Familial - 10%
Onset is usually > 60
Death within 5-10 years - due to infection, inanition or haemorrhagic stroke

47

What are the pathologies of ad ?

Atrophy of cortex- gyri shrink and sulci eidden and lose grey matter
Plaques and neurofibrillary tangles - start in enorhinal cortex-hippocampus-parahippocampus-cingulate gyrus- cortex

48

What are the plaques in ad ?

Proteinacious structure
Made up of amyloid beta protein
Surround by dystrophic neurites- neuronal processes that show kinking and strange structure around plaques
Extracellular
Reactive gliosis around them

49

What are neurofibrillary tangles in ad ?

Flame like
Intracellular inclusions of hyperphosphorylated tau protein

50

What neurons are lost in ad ?

Cholinergic neurons
Lose nAChR and ChAT

51

What are the earliest symptoms of ad ?

Short term memory loss
Disorientation- time then place
Visuospatial orientation
Apraxia
Aphasia, anomia acalculia

52

What are the later symptoms of ad ?

Loss of social skills
Psychosis and paranoia/hallucinations/delusions
Bradykinesia/rigidity

53

What are the latest symptoms of ad ?

Mutism
Bedridden
Incontinence

54

How is ad assessed ?

Mini mental state examination

55

What is mild cognitive impairment ?

Can precede ad
Complaint of memory loss
Have intact activities of daily living

56

What is mild ad ?

Forgetfulness
Short term memory loss
Impaired daily actives
Loss of hobbies and interests
Repetitive questions

57

What is moderate ad ?

Progression do cognitive deficits
Dysexecutive syndrome
Further impaired daily activities
Emergence of behavioural and psychological symptoms

58

What is severe ad ?

Agitation
Altered sleep pattern
Assistance required for feeding, dressing and bathing
Established behavioural and psychological symptoms

59

What is very severe ad ?

Bed bound
No speech
Incontinent
Basic psychomotor skills lost

60

What are the causes of ad ?

Genetic
-trisomy 21- beta amyloid protein resides on this
- familial - ApoE4
Amyloid
- forms plaques Nd it's thought the build up of these causes death of neurons
Trauma
- risk with head injury or with hypoxia/anoxic episodes

61

What pathway forms amyloid beta proteins ?

The beta pathway not the alpha

62

What is the amyloid hypothesis ?

States that amyloid beta protein is overproduced in ad and will give rise to aggregates of the protein binding to itself and forming plaques which give rise to the excitotoxcity that causes the symptoms of ad