Neurodegenerative Disease Flashcards
0
Q
What is neurodegenerative disease a loss of
A
Cells in the brain and spinal cord
1
Q
What does neurodegenerative disease affect
A
nerve cells and glial cells
2
Q
List 4 diseases involving degeneration of CNS neurons
A
- Dementia
- Extrapyramidal disorders
- Ataxic disorders
- Motoneuron disorders
3
Q
Give examples of dimentia
A
- Alzheimer’s disease
- picks disease
4
Q
What is the most common version of dementia
A
Alzheimer’s disease
5
Q
Give examples of extrapyramidal disorders
A
- Parkinson’s disease
- Wilson’s disease
- Huntington’s chorea
- dystonia musculorum deformans
- hallervorden-Spatz syndrome
6
Q
Give examples of ataxic disorders
A
- friedreich’s ataxia
- cerebello-olivery atrophy
- cerebellar atrophy
7
Q
Give and example of motoneuron disorders
A
Motoneuron disease
8
Q
In which part of the brain does dementia cause degeneration of neurones
A
Cerebral cortex
9
Q
Which is the most common version of extrapyramidal disorders
A
Parkinson’s disease
10
Q
Which sort of movements is involved in diseases from extrapyramidal disorders
A
Involuntary
11
Q
Which sort of spinal disorder is linked with ataxic disorders
A
Cerebello spinal disorder
12
Q
How many people does Parkinson’s affect
A
1 out of 750 people (common)
13
Q
How many cases are there of Parkinson’s in the UK
A
100,000
14
Q
Which other disease is Parkinson’s more common than
A
Multiple sclerosis
15
Q
What does the prevalence of Parkinson’s increase with
A
Age
Reaching a max at about 70
16
Q
Is Parkinson’s an age related disease
A
Yes
But can get when young (40) but rare
17
Q
How many new cases of Parkinson’s are there each year in the UK
A
9000
18
Q
List Parkinson’s disease symptoms
A
- 4-8 Hz tremor of limbs
- rigidity of muscle tone
- difficulty initiating movement (akinesia)
- movements slow
19
Q
When is tremor of limbs at its worst
A
When anxious and resting
20
Q
When does tremor of limbs stop
A
When asleep
21
Q
Why don’t Parkinson’s disease px blink much
A
Due to rigidity of muscle tone
22
Q
How to Parkinson’s patients appear due to difficulty initiating movement
A
Appear frozen
23
Q
What do Parkinson’s disease symptoms result in
A
- deadpan expression
- stooped shuffling gait (increased muscle tone in back)
- pill rolling (between fingers & forefingers)
24
What is the cause of Parkinson's disease
It is idiopathic (don't know what caused it)
25
Between which groups is Parkinson's disease equal
Male & female
26
What is Parkinson's disease characterised by a loss of
Dopamine producing cells in the substantia nigra of the basal ganglia
27
What is the substantia nigra
A black area visible on a cut section of the midbrain which produces dopamine
28
What does the substantia nigra produce
Dopamine
29
What is the basal ganglia
5 pairs of nuclei
30
Where is the basal ganglia located
In the thalamus
31
What region is involved in motor control
Substantia nigra of the basal ganglia
32
What is the appearance of the substantia nigra in Parkinson's disease
Diminished (dark patch is reduced)
33
what is the aim of pharmacological treatments of parkinson's disease
increase dopamine levels
34
what is L dopa
a smaller version of dopamine
35
what happens if you just try to inject more dopamine
it won't work as it can't go through the blood brain barrier
36
what is L dopa a precursor to
dopamine synthesis
37
what is the most common treatment for parkinson's
administration of a precursor (L dopa) for dopamine synthesis (in the presence of a substance blocking its depletion outside the CNS)
38
what advantage has injecting L dopa instead of dopamine
L dopa has transporters that can go through the blood brain barrier
39
what must you also give when giving L dopa to a px
an inhibitor of the AADC enzyme
40
why must you give an inhibitor of the AADC enzyme when giving a px L dopa
so that the L dopa can go through the blood brain barrier from the periphery so that it can produce dopamine inside the brain
41
what is the name of the inhibitor of the AADC enzyme
carbidopa
42
what does carbidopa inhibit
it inhibits the enzyme which converts L dopa in dopamine
43
what happens when you give L dopa & carbidopa at the same time
the dopamine isn't produced in the periphery
44
what ends up going through the blood brain barrier after L dopa & carbidopa are given at the same time
Ldopa
| carbidopa stays behind
45
what is the result of L dopa going through the blood brain barrier and carbidopa staying behind
the substantia nigra can produce dopamine with that L dopa
46
what is the advantage of inhibiting the enzyme which produces dopamine in the periphery
you can use much smaller quantities of L dopa to relieve symptoms of parkinson's
47
does L dopa cure the symptoms of parkinson's
no it only alleviates
48
does L dopa have an ongoing effect
no it becomes less effective after 5-7 years
49
name some other pharmacological ways of increasing dopamine levels
- direct agonists of dopamine by latching onto dopamine receptors & stimulate the neurones can increase the release of dopamine
- stop the destruction of dopamine as it is a monoamine so it can be destructed by monoamineoxidase therefore will have more dopamine around or it can stop the re uptake of dopamine
50
what is the most powerful pharmacological way of increasing dopamine levels
increasing the availability of L dopa
51
what side effects can pharmacological treatments for parkinson's cause
ocular side effects
52
list some non-pharmacological (therapies) used to treat parkinson's
- implantation of foetal tissue
- implantation of modified fibroblasts
- xenotransplantation
- adult stem cell culture and implantation
- glial derived neurotrophic factor (GDNF)
- electrical stimulation of basal ganglia by implanted electrodes
- gene therapy
53
how does implantation of foetal tissue work as a therapy to treat parkinson's
take parkinson cells from a baby and put into an adult brain but hasn't worked well
54
how does the implantation of modified fibroblasts work as a therapy to treat parkinson's
can be genetically modified to produce dopamine and but into brain
55
how does xenotransplantation work as a therapy to treat parkinson's
transplantation from other species such as pigs
56
how does adult stem cell culture and implantation work as a therapy to treat parkinson's
re programme stem cells to produce dopamine and put into substantia nigra
57
how does glial derived neurotrophic factor (GDNF) work as a therapy to treat parkinson's
substances produced by glial cells which help neurones survive.
can implant a pump into the abdomen which have these glial derived neurotrophic factors and occasionally pump it into the brain and into the substantia nigra to keep dopamine producing cells going
58
how does electrical stimulation of basal ganglia by implanted electrodes work as a therapy to treat parkinson's
by implanting electrodes into basal ganglia and inject electricity through them to produce dopamine
59
how does gene therapy work as a therapy to treat parkinson's
genes are out into people to replace the defective gene by putting the gene into viruses which get into the dna to produce dopamine
60
why are the effects of parkinson's on vision likely to be retinal in origin
- the basal ganglia are primarily motor
- dopamine is a neurotransmitter/neuromodulator in retinal amacrine and interplexiform cells (so dopamine is found in retina)
- in parkinson's disease levels of retinal dopamine are decreased
- parkinson's disease is also associated with abnormal ERGs
61
what is the basal ganglia involved in instead of vision
involved in movement so it won't effect vision directly
62
why is retinal activity changed in parkinson
due to lack of dopamine in the retina with parkinson's disease
63
name some visual deficits in parkinson's disease
- possibly decreased (low contrast) acuity
- abnormal saccadic and smooth pursuit eye movements (increased latency & reduced speed)
- decreased blinking
- large light adapted pupil. possible anisocoria. speed and amplitude possibly decreased
- longer latency and altered waveform of ERG and VEP - reduced temporal resolution
- possible triton colour defect (in blue pathway so tritanopic, associated with Alzheimer's)
64
which sort of visual functions are unaffected in parkinson\s disease
visual fields
65
how can akinesia (difficulty of movement) be alleviated
- by placing visual stimuli infant of the feet so px has something to aim for when walking
67
what can lead to akinesia (frozen movement)
irrelevent peripheral visual stimuli eg door frames inhibits movement
68
at what age does Alzheimer's disease usually occur
>70 years old
69
how many % of people over age 60 does alzheimer's disease effect
2%
70
how many % of people over age of 80 does alzheimer's disease effect
20%
71
what is alzheimer's disease characterised by
- loss of memory
- severely impaired judgement
- loss of emotional control
- eventually complete breakdown of mental function
72
how many phases does the progression of alzheimer's have
three
73
describe phase 1 of alzheimer's
- characterised by a slow deteriorating memory
- a feeling of disorientation in time and space
- inability to perform more complex tasks
- may get mood swings
- depression
- restlessness
- inability to sleep well
- disease may not be obviously apparent
- can last 5 years on average
- lose memory from recent things but can remember old things
- is not a bad stage when doing regular things e.g. making tea
74
describe phase 2 of alzheimer's
- more rapid
- deterioration of intellect and competence become more obvious
- blunting of emotions and apathy
- may get visual agonises (can't recognise faces)
- and dysphasia (use wrong words which are not understandable)
- possibility of delusions and hallucinations
75
describe phase 3 of alzheimer's
- represents the terminal stage
- may get epileptic fits
- general increase in muscle tone resulting in unsteady gait
- eventually become bed ridden
- and incontinent
- complete loss of personality
- patient fades away
76
what can the total duration of alzheimer's be
6-8 years
77
what type of disease is alzheimer's
terminal disease
| so can end up dyeing from it
78
which risk factor of alzheimer's has a strong genetic component
family history of alzheimer's disease 3.5%
79
list the risk factors of alzheimer's and state the relative risk in %
1. family history of alzheimer's 3.5
2. family history of down's syndrome 2.7
3. previous head trauma
males 2.67
females 0.85
4. family history of parkinson's disease 2.14
5. depression 1.82
6. maternal age 40+ 1.7
7. epilepsy 1.6
8. encephalitis/meningitis 1.6
9. herpes zoster/simplex 1.15
10. general anaesthesis 1.0
11. alcohol 1.0
12. immune diorders, oesteoarthiritis, poliomyelitis, thyroid disease, headaches, smoking, solvent exposure, head injury, blood transfusion <1.0
80
list the neuropathology of alzheimer's
- thinning of the cortex
- sulci have widened
- gyri have thinned
- loss of tissue may be most severe in frontal and temporal lobes
- brain has less bulk
- ventricles are enlarged
- deposition of amyloid beta-protein in the form of 'senile plaques' (5-200um)
- and formation of neurofibrillary tangles
81
what is the difference of brain mass from a normal individual to an individual with alzheimer's
1350gms - 1000gms
82
which levels of neurotransmitter are reduced in presynaptic in alzheimer's
acetylcholine
83
which neurotransmitter receptors are intact in postsynaptic region
acetylcholine receptors
84
is there a proven drug therapy for alzheimer's
no
85
how does alzheimer's affect the retina
reduction in retinal ganglion cells & thinning of nerve cell layer&lose magno cells
86
how does alzheimer's affect the optic disc
- disc pallor
- optic atrophy
- disc cupping in the absence of open angle glaucoma in some patients
87
how does alzheimer's affect the optic nerve
- decline in nerve axons
| - preferentially affecting the large diameter axons (Magno cell pathway)
88
how does alzheimer's affect the lateral geniculate nucleus
- accumulation of lipofuscin
| - resistant to tangle (NFT) formation
89
how does alzheimer's affect the suprachiasmatic nucleus
- degeneration reported in some patients
| - has lot of tangles and plaques in alzheimer's px so affects sleep patterns
90
where is the suprachiasmatic nucleus found
just above the optic chiasm
91
how does alzheimer's affect the visual cortex
- rarely atrophic
- myelin reduced in outer laminae
- loss of pyramidal cells
92
how does alzheimer's affect the B17 region
numerous cored senile plaques but few tangles
| pre stiate cortex affected
93
how does alzheimer's affect the B18 region
numerous neuritic senile plaques and tangles
94
what affect does the release of acetylcholine by the parasympathetic nervous system have on the iris sphincter muscle
constriction
95
how do alzheimer patients' pupils respond to light
it constricts less due to reduced levels of acetylcholine
96
how does tropicamide affect an alzheimer's px
they are more sensitive to it which can prove that they have less acetylcholine
97
what other visual test is possible for early alzheimer's identification
- evidence indicates that in the early development of alzheimer's, beta-amyloid protein gets deposited in the lens forming a cataract behind the iris
- the level of amyloid proteins in the brain is reflected by the size of the lens deposit
- the cataract is apparent a significant amount of times before dementia develops
