Neurodegenerative

Question 1

What is Neurodegenerative Disease?

Answer 1

It is the degenerative diseases to the neuron system including both the nerve cells and glia cells.

Question 2

What are the 4 groups diseases involved in degeneration of CNS neurons, classified into?

Answer 2

1. Dementia - Degeneration of neurons in the cerebral cortex. E.g. Alzheimer’s disease
   
   2. Extrapyramidal disorders - To do with involuntary movements. E.g. Parkinson’s disease
   3. Ataxic Disorders - cerebello-spinal degeneration. E.g. Frieddrecich’s ataxia

Montoneuron disorders - E.g. motoneuron disease

Question 3

What 2 most common diseases seen in practice that have visual disturbance?

Answer 3

1. Alzheimer’s

Parkinson’s disease

Question 4

How many people does Parkinson’s disease affect?

Answer 4

1 in 750 people

Question 5

What are the symptoms of Parkinson’s disease?

Answer 5

• 4-8Hz tremor of limbs (low frequency tremor) - especially the head, worse when resting/anxious, however when moving tremor not so band and goes at sleep.
  
  • Rigidity of muscle tone
  • Difficulty with initiating movement (akinesia) - appear frozen or just have difficulty moving.
  • Movement slow

Question 6

What is the pathology of Parkinson’s disease?

Answer 6

PD is due to low levels of Dopamine in part of the brain know as the Basal Ganglia

Question 7

Explain the treatment for Parkinson’s disease?

Answer 7

The main treatment is a pharmacological treatment
• The aim is to increase the dopamine levels

The most common treatment is administration of precursor for dopamine synthesis (in the presence of a substance blocking its depletion outside the CNS

Question 8

List the 5 ways to increase dopamine in the brain?

Answer 8

1. Agonists to stimulate postsynaptic dopamine receptors
   
   2. Facilitating dopamine release
   3. Preventing the breakdown od dopamine by monoamine oxidise
   4. Blocking the re-uptake of dopamine
   5. Increasing the availability of L-DOPA
      • Drugs that work in other ways e.g. steps 1-4 can be used when L-DOPA losses its effectiveness.

Question 9

Explain the use of L-DOPA to treat Parkinson’s disease:

Answer 9

Dopamine is a big molecule. It cannot be injected intravenously because it will not cross through the blood brain barrier.

Therefore you give L-Dopa instead which is a precursor to dopamine. This can cross the blood brain barrier because it has channels in which it can cross.
L-DOPA is converted into dopamine by an enzyme called AADC, which if found everywhere in the body.

Question 10

What is Cabidopa and what does it do?

Answer 10

a drug that inhibits the enzymes which converts L-DOPA to dopamine. It doesn’t cross the blood brain barrier only L-DOPA does. Then you get the L-DOPA into the brain –> the substantia nigra can make move dopamine.
So you can use much smaller quantities of L-DOPA to relieve the symptoms of Parkinson’s disease, because you inhibit the enzyme which turns it into dopamine in the periphery of the body.

Question 11

What are some of the Non-pharmacological treatments for Parkinson’s Disease?

Answer 11

1. Implantation of foetal tissue
2. Implantation of modified fibroblasts to produce dopamine and put into the brain
3. Xenotransplantation - foreign transplant form other species like pigs = take dopamine cells from.
4. Adult stem cell culture and implantation - stem cells to produce dopamine and put them into the substantia nigra
5. GDNF - Substances produced by glia cells which helps neurons survive
6. Electrical stimulation od basal ganglia by implanted electrodes

Question 12

Explain the ocular effects of Parkinson’s Disease?

Answer 12

The effects PD in vision is likely due to low levels of dopamine in the eye
With any affects of PD on vision are likely to be retinal in origin because:
• The basal ganglia are primarily motor
• Dopamine is a neurotransmitter or neuromodulator in retinal amacrine and interplexiform cells
• In PD levels of retinal dopamine are decreased
• PD is also associated with abnormal ERG’s
Some of the visual deficits in Parkinson’s disease include…
• Decreased (Low contrast) acuity
• Parkinson’s is a motor disorder and so eye movements are disrupted and slower, and a latency before they start tends to be increased
• Decreased blinking
• Large light adapted pupil. Possibly anisocoria. When the pupil does respond it is slow and not as much
• There may be colour vision defect - Tritan = defect of the blue cone pathway.
Akinesia (frozen movement) is often experienced by PS patients
• This can be alleviated by visual stimuli placed in front of the feet
• Irrelevant peripheral visual stimuli e.g. Door frames can lead to akinesia. E.g. cant seem to get though a door = irrelevant visual stimuli in the periphery seems to inhibit the movement

Question 13

What is Alzheimer’s Disease?

Answer 13

AD is characterised by loss of memory, severely impaired judgment, loss of emotional control and eventually results in a complete breakdown of mental function. It is a terminal disease and likely to die form it unless something else kills you before it. It is a progressive disease and it has 3 phase.

Question 14

What is Phase 1 of Alzheimers disease?

Answer 14

• Forget recent things but remember stuff form a long time ago
  
  • Disorientation of time and space e.g. don’t know what day of the week it is
  • Inability to perform more complex tasks
  • Maybe get mood swings, depression, restlessness and inability to sleep well
  • Disease may not be apparent

Question 15

What is phase 2 of alzheimers disease?

Answer 15

• No longer know their ill
  
  • Visual Agnosia - can’t recognise faces
  • Dysphasia - don’t put words in the right order
  • Delusions and hallucinations

Question 16

What is phase 3 of Alzheimers disease?

Answer 16

• Terminal phase
  
  • May get epileptic fits
  • Muscle ton increases so you shuffle around slowly
  • Personality ‘fades’ away

Question 17

Explain the neuropathology of Alzheimer’s disease:

Answer 17

• Thinning of the cortex. Sulci have widened and gyri thinned. Loss of tissue may be most severe in the frontal and temporal lobes.
  
  • Ventricles also enlarge in AD
  • In general the brain weight in AD patients has decreased from the 1350gms to 1000gms
  • AD is characterised by the deposition of amyloid B-proteins in the form of ‘senile plaques’ and the formation of abnormal ‘neurofibrillary tangles’.

Question 18

What neurotransmitter is affected in Alzheimer’s disease?

Answer 18

• The main neurotransmitter is affected in Alzheimer’s disease is Acetylcholine.
  
  • People with Alzheimer’s disease have lower levels of Ach
  • Other neurotransmitters are affected too but Ach is the main one.
  • Receptors in acetylocholine are intact, so it’s a pre-synaptic loss of ach, thus you can’t just give it to people ach to cure it.
  • This means there is no cure for Alzheimer’s disease.
  • However, there are some drugs that might help improve memory.
  • There is a clinical trials, to sniff a drug which stimulates microglia.
  • Microglia are glia cells in the brain that phagocytes and go round eating amioly protein planks. But this is still in clinical trial at the moment.

Question 19

Explain how Alzheimer’s disease can affect vision:

Answer 19

There are changes in the visual pathway in Alzheimer’s disease and therefore this affects vision.
Example: In the retina there are fewer ganglion cells so the optic nerve gets thinner. Some say the optic disc has changes such as the optic disc pallor and a bit of atrophy. If the optic nerve gets thinner then you lose m-cells = magno-celluar, which are bit cells responsible for coding and luminance.
Other examples include the LGN building up of Lipofuscin and the Superchiasmatic Nucleus (located above the chiasm) which is involved in regulating our circadian rhythms - when to sleep and wake up, however, in people with Alzheimer’s they have poor sleep patterns due to the degeneration of this nucleus

Question 20

How can you diagnose/test Alzheimer’s disease?

Answer 20

At present the only way to diagnose is to cut up the brain and observe. But this will mean people will have to be dead in order to do this.
However there are various stains available with imaging dine with PET scans.
• The other way is though Optoms - take the pupils for example. The pupils are a sphincter muscle innervated by the parasympathetic nervous system and releases Ach causing it to constrict. Alzheimer’s is characterised by a decrease in Ach levels and so in response to light the pupils of AD constrict less.
• People with Alzheimer’s disease may have a hypersensitivity to Tropicomide . This drug dilates pupils and blocks Ach receptors, so if you don’t have much Ach anyways; you need less Tropicmide to block receptors. So another test or Alzheimer’s disease is to see how sensitive people are with Tropicmide - the more sensitive they are the less Ach they have and so more likely to have Alzheimer’s disease .
• An easier thing to use would be a form of Cataract B-amyloid protein which gets deposited in the brain which then is reflected by the size of the lens deposit, forming a cataract behind the iris. Cataract in the lens is apparent way before you get dementia.