Parkinson's Disease L5 Flashcards Preview

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Flashcards in Parkinson's Disease L5 Deck (64):
1

What proportion of people are affected by a brain disease in their life?

1/4

2

What proportion of people are affected by Parkinson's disease?

between 1/1000 and 1/900
Victims aged 60 yrs
Due to aging population of occurring at a earlier age

3

What is Parkinson's disease?

Parkinson's disease is a Progressive disorder of the Central Nervous System CNS which typically affects victims aged about 60yrs old
Degeneration of dopamine producing neurons
This Degeneration is thought to be due to 2 reasons:
1. Absence of Dopamine production
2. Concentration between ACh : DA
Leads to the Degeneration of the DOPAMINERGIC NIGRO-STRIATAL PATHWAY

4

What sort of disorder is parkinson disease?

Progressive disorder
Can get worse with age and time
Can be Fast OR Slow progressive, - due to the variations of the Basal ganglia damage/affect
Dont tend to have clear symptoms until 60% of cells on one side of Snc have degenerated
-shows ability/extent that the brain can compensate : i.e. the degree of cell loss has to progress to quite a considerable extent before symptoms are obvious

5

Which pathway is degenerated in Parkinson's Disease?

Dopaminergic Nigro-Striatal Pathway

6

What are the exact causes of Parkinson's Disease?

Exact cause is Unknown
But there are 2x probably causes:
1. Toxic Chemicals
2. Inheritance

7

Can Parkinson's disease get worse?

Yes
1. with Age
2. with Time

8

What are the 5x characteristic symptoms of Parkinson's Disease?

1. Mood
2. Tremor
3. Rigidity
4. Bradykinesia
5. Hypokinesia

9

What does the characteristic Parkinsonian "Mood" symptom involve?

Problem conveying mood
Basal Ganglia damage/impairment
Basal Ganglia now unable to carry out Mood and Movement function
Emotionally flat
Unable to express emotions through muscular emotional expression
-accentuated by the rigidity of facial muscles due to increased tone causing increased Rigidity (another symptom)
Still feel all their emotions and are still intellectually switched on (although this can decrease with age), but can't express their emotions or control muscles
-is like living in a cage

10

What happens with involuntary contractions in Parkinson's disease?

Often, Involuntary Skeletal muscle contractions often INTERFERE with Voluntary movements

11

What does the characteristic Parkinsonian "Tremor At Rest" symptom involve?

Occurs at rest (will have it when sitting down)
Pill Rolling tremor
Muscles in the Upper Limbs may Alternatively Contract and Release, causing the Hands to shake
Starts on one side and proceeds to the other

12

What causes the Tremor at rest symptom of Parkinson's disease?

muscles in the Upper limbs starts Alternatively contracting and releasing, causing the hands to shake

13

What does the characteristic Parkinsonian "Rigidity" symptom involve?

Cogwheel rigidity - No smooth movement when trying to extend bent arm
Increased muscle TONE
causes Facial muscles to be rigid, leading to a Mask-like appearance
a. Unblinking stare
b. Slightly open mouth
c. Uncontrolled Drooling

14

What 3x things does the Characteristic Parkinsonian Facial Muscle Rigidity to give a Mask like appearance symptom involve?

1. Unblinking stare
2. Slightly open mouth
3. Uncontrolled Drooling

15

What does the characteristic Parkinsonian "Bradykinesia" symptom involve?

"Brady"= slow
"Kinesia" = movement
SLOW movements
Slow to Get Going and problems with Starting to Walk
-often get into gear, get Faster and Faster, and eventually Fall over
Motor-Performance is impaired (harder to get into gear - walking -things like shaving impaired)
Characteristic Stooped stance

16

What is the characteristic stance of a person with Parkinson's disease?

Stooped

17

What does the characteristic Parkinsonian "Hypokinesia" symptom involve?

"hypo"= smaller
"Kinesia" = movement
Smaller /Decreased Range of Motion of muscular movements
-Handwriting eligible
-Walking steps are smaller

18

What 2x things does the Characteristic Parkinsonian Hypokinesia symptom involve?

Smaller range of motor movement
1. Handwriting eligible
2. Smaller steps when walking

19

Are the symptoms Fast or Slowly progressive in Parkinson's Disease?

"Parkinsonian's"
Can be wither Fast or Slowly progressive
due to the range/variations of damage of the Basal Ganglia (dependant/individual to each patient)

20

What are the main 4x categories of Parkinson's Disease Treatment?

1. Drug
-a. L-DOPA
-b. Cholinergic Drugs
2. Surgical Lesions
-a. Pallidotomy
-b. Thalamotomy
3. Electrode Stimulation
-a. Deep Brain Stimulation
4. New Novel Treatments
-a. Cell Replacement (Transplantation)
--i. Immature Neurons (fetal)
--ii. Genetically Engineered and cultured neurons
--iii. Embryonic stem cells
--iv. Adult stem cells (SV2)
-b. Gene Therapy (viral Vectors)

21

What are the 5 New Novel Treatments?

-a. Cell Replacement (Transplantation)
i. Immature neurons (fetal)
ii. Genetically engineered and cultured neurons
iii. Embryonic stem cells
iv. Adult stem cells (SV2)
-b. Gene Therapy (Viral Vectors)

22

What does the Cell Replacement (Transplantation) New Novel Treatment involve?

Involve the transplantation of Dopamine producing cells
However CANNOT transplant mature brain cells into the Striatum, they Must be Immature/Young

23

What are the 4x types of cell replacement transplantation therapy?

1. Immature Neurone (fetal)
2. Genetically Engineered and Culture Neurons
3. Embryonic Neurons
4. Adult stem cells (SV2)

24

What are features of the "Immature Neurons (fetal)" Cell Replacement (Transplantation) Treatment involve?

Transplantation of immature fetal neurons into the brain
Tested with rat foetuses and rat brains
3x types of problems
1. Major ethical issues:
- Aborted Fetuses - controversy/dependant on beliefs
2. Technical Issues
-10 weeks old
- keep cells alive
-have to abstract correct cells from a specific part of the foetus's brain
3. Potential for Tumours to form from the transplanted cells
-Cannot control if the cells multiply to form a tumour

25

What are features of the "Genetically Engineered and Cultured Neurons" Cell Replacement (Transplantation) Treatment involve?

Made in a lab to be Cells which Produce Dopamine

26

What are features of the "Embryonic stem cells" Cell Replacement (Transplantation) Treatment involve?

Embryos at 4 days old

27

What are features of the "Adult Stem Cells (SV2)" Cell Replacement (Transplantation) Treatment involve?

Discovered that Humans still have Neural Stem cells in the SubVentricular zone (SV2), which lies along ventricular margin
they are left over from when was a nucleus
Medial to the cuadate nucleus, Central
These adult stem cells Keep making brain cells forever
found in both rats and humans
Evidence that Increasing exercise leads to an Increased number of brain cells being are Produced by these brain stem cells
--> need these New brain cells to replace those lost due to the brain disease
NO ETHICAL problems (in own brain and are their own cells)
BIOPSY, modify stem cells in a lab to make, transplant into the striatum of the cell's same patient

28

What does the Gene Therapy (Viral Vectors) New Novel Treatment involve?

Viral Vectors for making GABA (increased inhibition)
Inserting genes such as gene for Dopa-decarboxylase, which makes GABA
Insert into the SUT (SUbThalamic Nucleus)
INHIBITS cells in the SUT (due to GABA)
- Leads to Decreased activity of the GPi or Other cells which Make Dopamine
- Quietens down the over activation of GPi in Parkinson's disease

29

What does the Electrode Stimulation Deep Brain Stimulation Treatment involve?

Initially used as reassurance to check that the electrode was in the correct area for surgery, and wasn't affecting parts of the corticospinal tract
Found that by stimulating cells in the GPi lead to an Improvement of symptoms
GPi Inititially
SUT Subthalamic Nucleus currently
Electrode is attached (to GPi or SUT), bought through Skull and down into Chest
Frequency and Amplitude can be altered via a Remote Control (Pacemaker Stimulator)
able to Vary the quantity of Stimulation - to the patient's Individual Needs/Case
Wire is Gold and Insulated
Is Reversible (not irreversible like surgical lesions/freezing) - Isn't killing cells
Really good for patients with Tremor (at rest)
However NOT effective for ALL patients
Done on ONE side of the brain
- Deep brain stimulation on both sides of the brain can lead to Complications/Speech Disorders
Empirical Treatment - don't know why it works, surgical lesion and stimulation seem to be the opposite treatments, but stimulations works too

30

What is the wire for Deep Brain Stimulation like?

Gold and Insulated

31

What side of the brain is Deep Brain Stimulation done on?

ONE side of the brain
-both sides deeply stimulated = complications
--e.g. Speech Disorders

32

What is an example of an Empirical treatment?

Deep brain stimulation
don't know why it works, lesion and stimulation seem to be the opposite treatments, but stimulations works too

33

What is the effectiveness of Deep Brain Stimulation like?

Really good for patients with Tremor (at rest)
NOT effective for ALL patients

34

What are the 2x types of Surgical Lesion Treatment's for

1. Pallidotomy - Lesion of the GPi
2. Thalamotomy - Lesion of the Thalamus

35

What does the Surgical Lesion Pallidotomy Treatment involve?

First surgical Lesion Parkinson's treatment discovered
GPi
Involves Killing (Irreversible) of neurons in the GPi
Stop's the Gpi over activation
Inserts Freeze tip Electrode Probe into the brain to Stop the Impulse conduction
-kills cells in centre permanently (irreversible), cells on outside edge of lesion recover
Continue until Tremor went away
Done under Local Anaesthetic into the Skull - as brain has no sensory nerves/doesn't feel pain - so patient is Awake and has VALIUM for slight sedation
Valium so is Quieter and Less Anxious whilst Remaining conscious
Very invasive
IRREVERSIBLE
must be Very Precise
- as it is close to the Optic nerve (- beneath Gpi), corticospinal tract and Internal Capsule
- and GPi is very small
Very important that patient is awake: as can continue until the tremor disappeared, and patients can't speak if Broca's area is affected ad will know this)- will know if something has gone wrong (Loss of vision or Major stroke)
-Precision increased with development of MRI and Visual Imaging Technology --> as imaging has improved Pallidotomy has become preferred
Performed on ONE side only (two side surgical lesion = complications and speech problems)

36

What is the GPi close to that is of major concern during Surgical Lesion Pallidotomy Treatment?

Beneath is Optic Nerve (vision) --> damage = losing vision
Corticospinal Tract -large --> damage = major stroke
Internal Capsule -large --> damage = major stroke

37

What does the Surgical Lesion Thalamotomy Treatment involve?

Second Surgical Lesion Operation developed
Thalamus (VAVL nucleus)
-Targeting the Processing Area (thalamus)
Involves Killing cells (irreversible) in Thalamus (VAVL nucleus)
affects the Out from Gpi at axon terminals
Very Invasive
But BIGGER Target= therefore DECREASED RISK of other complications
Involves placing a Freeze Tip Electrode into the brain and making a Lesion into the VAVl nucleus of the thalamus
Thalamotomy Stops the Increased Inhibition of UMN (original due to GABA release due to the Abnormal activity of the GPi) via Targeting the Recessing Area (i.e. the Thalamus)
However as imaging improved PAllidotomy becomes preferred

38

What does Thalamotomy target?

Thalamus (Va-VL)
the processing centre

39

What does Pallidotomy target?

GPi

40

Which Parkinson's treatments are irreversible?

Pallidotomy
Thalamotomy
-both form lesions via free tip electrode
Permanently Irreversibly kills the cells in the centred of the lesion, the cells on the edge of the lesion recover

41

Which Surgical Lesion Treatment is preferred?

Pallidotomy
esp because now there is MRI/Visual Imaging Technology which increases the precision

42

What Surgical Lesion Treatment has a smaller risk?

Without MRI and Visual Imaging Technology, Thalamotomy is Less risk as the Thalamus is larger than the small GPi

43

What leads to perfect movement?

Balance of the two neurotransmitters
GABA : inhibitory - from GPi
Glutamate : Excitatory - from Cerebellum (small brain) Cerebellar System

44

What are the 2x Drug Treatments for Parkinson's Disease?

1. L-DOPA
2. Cholinergic drugs

45

What are features of Cholinergic Drug Treatment for Parkinson's Disease?

being utilised alongside L-DOPA
bleeding in brain = weakness in brain wall = haemorrhage

46

Why doesn't Dopamine Tablets work?

Dopamine in it Putative form is Unable to be Absorbed in the blood and to cross (CANNOT cross) the Blood-Brain-Barrier
Blood brain barrier (blood --> brain) = the barrier for substances entering the brain
They have no affect as the dopamine tablets are broke down by the stomach, and is Delivered in Another form other than dopamine

47

What are features of the L-DOPA Dopamine Replacement Treatment for Parkinson's Disease?

L-DOPA is a PRECURSOR to dopamine
Can cross the Blood brain barrier and therefore Can reach the brain (isn't broken down in the stomach)
Once it reaches the brain it is then converted into dopamine
It is One Metabolic Step away from being converted into dopamine by Dopamine-DeCarboxylase
Dopa-Decarboxylase is found in the Snc
Effective treatment
Increased dopamine levels counteract the amount of Snc dying which no longer produce dopamine normally
INITIALLY is miraculous - with just small dosages
Often Given with other Compounds in order to Prolong its effects in the brain
ISNT a Long-term treatment - as it requires Increased Dosages as time progresses
-if long term can lead to Side effects : Nausea and vomiting
-EXCESS L-DOPA can cause DYSKINESIA
Dyskinesia is abnormal, uncontrolled, involuntary and potentially continuous movement, which can actually be worse than the original disease
Side effect of Increased Toxicity
Problem: ness to increase the dosage due to the cells dying, but the Side Effects are increased Toxicity
Also possible that could Hasten the Degeneration of Remaining Dopamine producing Snc cells
Sometimes not the best reattempt for some patients
Some Patients react differently -due to the dopamine flooding and effecting all parts of the brain. there are only 3-4 pathways which actually use Dopamine as neurotransmitter but this variation can lead to Different Side effects in Different Patients

48

What is Dopa-decarboxylase?

Enzyme found in the Snc Substantia Nigra Pars Compacts
and is the enzyme which converts the dopamine precursor L-DOPA into Dopamine

49

Where is Dopa-decarboxylase found?

Snc Substantia Nigra pars compacta

50

How do you prolong the effect of L-DOPA in the brain?

Give L-DOPA in combination with other compounds, to prolong its effect in the brain

51

What is dyskinesia?

Abnormal, uncontrolled, involuntary, and sometimes potentially continuous movement
caused by Excess L-DOPA (usually due to long term use and need for increased dosages)
Can actually be Worse than the original disease

52

What are the 4x Negatives to L-DOPA Dopamine Replacement Treatment for Parkinson's Disease?

1. Side effects - nausea and vomiting
2. Increased dosage Long term causes increased toxicity
3. Dyskinesia - abnormal uncontrolled involuntary and sometimes continuous movement
4. Hasten the degeneration of remaining dopamine producing cells/still functional neurons which can still produce Dopamine

53

Are the treatments learnt used exclusively for Parkinson's disease?

No
helps a variety of brain diseases

54

What are the characteristic Biological features of Parkinson's disease?

Snc affected in the Midbrain
Normally Fine and Lightly myelinated fibres from the Snc terminate in the striatum and release Dopamine made in the Snc
Dopamine travels along the Dopaminergic Nigro-Striatal Pathway
-(constant production of dopamine. Dopamine levels cary up and down. Always a high concentration of Dopamine in the striatum)

But with the Snc cells dying there is Decreased number of Pigmented cells
This leads to a Decreased production of the Dopamine Neurotransmitter in the Snc
This changes the Output of cells projected to the GPi and SUT
Less Dopa
GPi cells become HYPERactive/Tonically active, and begins Firing continuously, releasing Large amounts of Inhibitory GABA into the Thalamus, which Decreases the information and number of impulses (via decreased Frequency and decreased intensity), leading to Decreased Excitation(increased Inhibition) of UMN, and therefore patient shows Slow moments, and difficulty initiating movements

55

What happens to cells in the GPi in Parkinson's disease which leads to Slow movements and Difficulty initiating movement?

GPi cells become HYPERactive/Tonically active, and begins Firing continuously, releasing Large amounts of Inhibitory GABA into the Thalamus, which Decreases the information and number of impulses (via decreased Frequency and decreased intensity), leading to Decreased Excitation(increased Inhibition) of UMN, and therefore patient shows Slow moments, and difficulty initiating movements

56

What are some features of Dopamine?

Various effects - Cells in Striatum, dopamine causes inhibition in come cells and excitation in other stratal cells
Due to different types of receptors: D1 and D2 receptors
Therefore doesn't either a excitatory or inhibitory property

57

What can occur before a person has parkinson's disease?

Before First symptoms become clear cut
Years Prior
60% of cells on One side have become Degenerated
-shows the complexity of such brain conditions
-shows the extent to which the brain can compensate for damage
- shows that the degree to which cells loss has to progress to is quite a considerable extent before symptoms are obvious
Causes symptoms on opposite side
-can see slight tendency/symptoms years before but never distinct - is more just an after thought

58

What happens during Parkinson's Disease?

The degeneration begins on one side and goes to the other side

59

What side of the body is effected in comparison to the side of brain of Snc cells degeneration?

Symtoms occurs on opposite side of the body (tremor at rest, mood, rigidity, bradykinesia and hypokinesia) to the Snc cells degeneration

60

What does the delayed clear cut symptoms of Parkinson's disease even though there is 60% brain degeneration show?

-shows the complexity of such brain conditions
-shows the extent to which the brain can compensate for damage
-shows that the degree to which cell loss has to progress to in order for symptoms to become obvious is quite considerable

61

How is Tonic activity controlled?

Tonic activity is reigned up and down by Glutamate

62

What are the 9x key steps that occur when there is Parkinson's disease in the cells?

1. Loss of Snc cells
2. Loss of Dopamine
3. Gpi cells are more excited than normal (as dopamine is inhibitory on Gpi cells)
4. OVeractivation of Gpi GABA release - due to Hyperactive Gpi cells
5. Increased GABA inhibits cells communicating between the Thalamus and Motor Cortex
6. Decreased excitation of the Cerebellum
7. More inhibition of UMN in Motor Cortex
8. Less impulses (in frequency and intensity) To and From the UMN
9. Less UMN activity = Slower and more Gradual movements
Issues:
a. starting movement : due to Basal Ganglia damage
b. Tremor at rest : possibly due to the oscillation of the Thalamus

63

What is the issues of initiating movements in Parkinson's disease likely to be directly due to?

Damage to the Basal Ganglia

64

What is the issue of Tremor at rest in Parkinson's ease likely to be due to?

Possibly due to the Oscillation of the Thalamus