Neurol - MedEd - Tremour

Question 1

Movement disorders can be divided into…

Also provide examples

Answer 1

Hypokinetic disorders - Parkinson’s

Hyperkinetic disorders - Essential tremour

Question 2

What is Parkinson’s - pathophys

Answer 2

Loss of dopaminergic neurons in substantia nigra

-Think of dopamine as GAS and ACh as the BREAKS

Question 3

What does dopamine do in substantia nigra?

Answer 3

Dopamine binds to D2 receptors
Which inhibits GABA (inhibitory)
- so disinhibits GABA –> creates movement

Question 4

What does ACh do in substantia nigra?

Answer 4

ACh stimulates GABA to inhibit movement

Question 5

What happens to levodopa in the body?

Answer 5

1) Levodopa breaks down to dopamine in periphery –> which cannot get past BBB
2) Levodopa can be broken down to other products by enzyme COMT
3) Levodopa can cross BBB –> converts to dopamine in the brain (good!) –> stimulates D2 receptors

Question 6

What is the metabolism of dopamine in the brain?

Answer 6

To products
DOPA-C by MAO-B
3MT by COMT

Question 7

Dopamine in other tracts of the brain (not the substantia nigra) can cause… (we cannot control where dopamine goes)

Answer 7

Psychosis

Question 8

Parkinson’s - 4 main symptoms

Answer 8

1) Bradykinesia - trouble getting started
2) Cogwheel rigidity - not fluid when testing strength
3) Resting tremour - pillrolling
4) Gait or postural instability
(can also have dementia and autonomic instability)
-Mask-like faces, pillrolling, shuffling gait

Question 9

Parkinson’s diagnosis

Answer 9

Clinical!

Can get brain imaging: CT (not helpful), MRI will show degeneration of substantia nigra

Question 10

Treatment of parkinson’s

Answer 10

1) ACh antagonists - benztropine - used in young ppl with mild disease
2) Amantadine - in the past, not used anymore!
3) COMT inhibitors - capones
4) MAO-B inhibitors - selegeline
5) Levodopa with carbidopa - carbidopa inhibits breakdown of levodopa in the periphery
Carbidopa cannot cross BBB, so allows levodopa to be converted to dopamine in the brain
6) Dopamine agonist - ropinirole, pramipexole (bromocriptine)

Question 11

What to do with patients who have signs and symptoms of Parkinson’s? What is the treatment tree?

Answer 11

Age and functional?

• If less than 70 AND functional –> Dopamine agonist
• If > 70 or dysfunctional –> Levodopa and carbidopa
• The more levodopa/carbidopa is used, the less effective as neurons degenerate in s.n. –> so this is where add COMT inhibitors and MAO-B inhibitors - give them functionality as long as possible
• If all meds fail –> try deep brain stimulation

Question 12

Essential tremour - pathophys

Answer 12

Familial

Question 13

Essential tremour - what is it?

Answer 13

Occurs with use
No tremour at rest
Usually male, middle-aged

Question 14

Essential tremour - diagnosis

Answer 14

Clinical

Question 15

Essential tremour - treatment

Answer 15

Low-dose nonselective BB - propranolol

Question 16

Intention tremour - pathophys

Answer 16

Cerebellar dysfunction

-Stroke or alcohol

Question 17

Intention tremour - what is it?

Answer 17

No tremour at rest

Is a tremour at movement - worsens with closer to target!

Question 18

Intention tremour - diagnosis

Answer 18

Clinical

-i.e. stroke on MRI

Question 19

Intentional tremour - treatment

Answer 19

No treatment, due to cerebellar destruction

Question 20

Huntington’s - pathophys

Answer 20

Trinucleotide repeats
Anticipation - appear at a younger age with each generation
Autosomal dominant

Question 21

Huntington’s - symptoms

Answer 21

Chorea - purposeless ballistic movements

Psychosis, depression

Question 22

Huntington’s - diagnosis

Answer 22

Clinical

Question 23

Huntington’s - treatment

Answer 23

None