8.2 Parkinson’s Disease

Question 1

Define Parkinsonism

Answer 1

Umbrella term for symptoms of Parkinson’s

Question 2

What are the 4 cardinal features of parkinsons? (TRAP)

Answer 2

Tremor, Rigidity, Akinesia (bradykinesia), Postural instability

Question 3

Describe the postural appearance of someone with parkinsonism and explain why

Answer 3

Stooped posture, spine bent forward and legs flexed. This allows the person to stay upright by overcoming the lack of back muscle function due to the bradykinesia. The knee flexion is a result of the stooped posture to compensate for lack of back muscles, NOT a symptom of Parkinson’s itself.

Question 4

What is meant by a ‘masked face’ in a patient with parkinsons?

Answer 4

Masked face, because muscles don’t get activated often patients appear as if they are wearing a mask… ‘appear emotionless’. Reduced blinking is also seen

Question 5

Describe the GATE of a patient with parkinsons

Answer 5

Short shuffling gate, ‘Akinesia’ (‘Braykinesia’ because there is some movement)

Question 6

What is the defining feature of Parkinsons?

Answer 6

Bradykinesia (very specific to lack of dopaine in the basal ganglia)

Question 7

Give 4 possible causes/associations with parkinsons and highlight the MAIN one

Answer 7

1) Idiopathic: most common (95%)
2) Genetic (rare) both autosomal dominant and recessive types exist
3) Vascular: multiple white matter infarcts
4) Post-infectious: post encephalitic parkinsonism

Question 8

Name a medication that should NOT be given to a patient with Parkisnons and explain why

Answer 8

antiemetics, antipsychotics (dopamine antagonists)

In a patient with parkinsons, dopamine is already low and thus giving meds that block dopmine will put patient in a ‘parkinsonian crisis’ (extreme ridgidity and Akinesia)

Question 9

Overall what is the action of dopamine on the direct vs indirect pathway?

Answer 9

Dopamine has an overall excitatory effect on the direct pathway and an inhibitory effect on the indirect pathway

Dopamine is constantly acting on either pathway depending on the responce required/decided by the basal ganglia

Question 10

Describe the direct pathway

Answer 10

Question 11

Describe the indirect pathway (The NO-GO pathway)

Answer 11

Question 12

What releases dopamine in the motor pathway?

Answer 12

Substantia Niagra Compacta

Question 13

Describe how loss of dopamine in Parkinsons affects the NO-GO system

Answer 13

Loss of dopamine leads to an increase in inhibition of the basal ganglia onto the cortex. Hence, we no longer have the GO signal and thus we NO-GO ➞ bradykinesia

Question 14

What causes ‘Rigidity’

Answer 14

Tremor in muscles causes increased tone ➞ resistance to passive movement ‘cog-wheel’ ➞ rachet like interruptions

Creates a more flexed posture

Question 15

Compare the effect on muscles in Parkinsons vs UMN lesions

Answer 15

Parkinsons: Agonist and antagonist muscles affected equally

UMN rigidity: Is greatest at the start and called ‘clasp-knife’

Question 16

What is Akinesia (bradykinesia)

Answer 16

Slowness of voluntary movement due to a reduction in automatic movement – e.g arm swing when walking

Power retained

Question 17

Describe the features of a tremour seen in a patient with parkinsons

Answer 17

‘pill-rolling’ rhythmic flexion/extension of fingers, supination-pronation of forearm

Increases during stress and reduces on movement

This is a resting tremour!

Question 18

Describe the distribution of muscles affected in Parkinsons

Answer 18

Usually asymmetrical

Question 19

What 2 features of parkinsons causes the ‘cog-wheel’ movement?

Answer 19

Ridgity and Bradykinesia (start-stop-start-stop etc…)

Question 20

Why must we ask the patient to do BIG and FAST movements to elicit Bradykinesia

Answer 20

because we want to tire out their remaining dopamine. The remaining dopamine in the basal ganglia is able to provide some manner of go, but over time repetitive movements require a repeating go signal and dopamine is not an infinite resource hence, it is used up.

Question 21

How do we manage Parkinsons disease? (include the patho of the drug you have mentioned)

Answer 21

Nothing slows the progress of PD

Treatment of choice is dopamine replacement with levodopa ➞ L-Dopa + peripheral decarboxylase inhibitors

L Dopa is a precursor of dopamine which is converted both peripherally and centrally by decarboxylation. As the majority of dopamine is converted peripherally before it reaches the brain we need to block peripheral decarboxylase using dopadecarboxylase inhibitors.

Also, only the precursor form of dopamine can cross the BBB and thus using dopadecarboxylase inhibitors prevents conversion into dopamine untill it reaches the brain

Question 22

List 4 side effects of levodopa (L-dopa)

Answer 22

Nausea, hypotension, hallucinations, nightmares

Question 23

Prolongued use of levodopa (L-dopa) can lead to what?

Explain why this occurs and when it is most prevelant?

Answer 23

Dyskinesias begin to appear due to receptor hypersensitivity which is worse at beginning of dose

Question 24

Explain why the ‘on and off phenomenon’ of levodopa (L-dopa) occurs

When it is most prevelant

Answer 24

Worse symptoms occur at end of dose which can lead to ‘’on and off’’ phenomenon

This is because dopamine is stored in the brain and in early stages of disease one dose can last several hours

BUT after about 5 years brain loses ability to store dopamine so ‘’wearing off’’ occurs and doses become effective for shorter times

Question 25

Give an agonist of dopamine that can be given instead of dopamine

Answer 25

Pramipexole

Question 26

What 2 enzymes are involved in the breakdown of dopamine?

Give 2 drugs that inhibit each of these enzymes

Answer 26

MAO-B and COMT

MAO inhibitors (Rasagiline)

COMT inhibitors (Entacapone)

Question 27

Give one other drug that may be used in management of Parkinsons

Answer 27

antimuscarinics

Question 28

What is Huntington’s disease (incl its inherritance and mutation)

What is the average age of onset?

Answer 28

Progressive movement disorder with dementia

Autosomal dominant mutation of polyCAG on chromosome 4

Normal 20-40 adult onset

Question 29

What is seen in the cortex of a patient with Huntingtons?

Answer 29

Cerebral atrophy particularly in the cortex, caudate and putamen

Question 30

Describe the classical sign of Huntingtons

Answer 30

Progressive chorea: ceaseless rapid, jerky movements

(sign onset usually 30-40yrs old with death within 15yrs)

Question 31

Give 3 management options for Huntingtons disease?

Answer 31

1) Psychological support
2) Antipsychotics
3) Tetrabenazine

** No treatment

Question 32

What is Wilsons disease? (incl its inherritance)

Give 3 clinical features

Answer 32

Autosomal recessive disorder of copper metabolism.

If untreated causes neurological and hepatic dysfunction because copper accumulates in the basal ganglia, liver and eye

Clinical features: diverse

• Kayser-Fleischer rings
• Liver failure
• Parkinson’s–like tremor, dysarthria

Question 33

What would be seen in an investigation of Wilsons?

How would you treat?

Answer 33

Investigations: raised urinary copper, reduced caeruloplasmin (carries Cu2+ around) and reduced serum copper

Treatment: penicillamine which chelates copper and increases excretion

Question 34

Give 3 other important movement disorders

Answer 34

1) Benign essential tremor: tremor seen in fine movement
2) Dystonias: abnormal state of sustained muscle contraction
3) Parkinsonism: various drugs antagonise the dopamine receptors (This is really important!)

Question 35

Give 5 types of Dystonias

Answer 35

1) Cervical dystonia
2) Writer’s cramp
3) Blepharospasm
4) Tic syndromes
5) Drug induced: antipsychotics, haloperidol, metoclopramide

Question 36

What is Wernicke encephalopathy and what is the triad of symptoms seen

Answer 36

Cerebellar disorder caused by a Thiamine (vit B1) deficiency

Commonly seen in chronic alcoholics

Triad CF:

1. Confusion
2. Ophthalmoplegia (eye muscle paralysis)
3. Atxia (no muscle control)

Question 37

What can vertebrobasilar insufficiency (problem with basilar arteries) lead to?

Answer 37

Cerebellar infarct ➞ Ipsilateral limb ataxia, lateropulsion and hypotonia

Question 38

List 4 common causes of cerebellar disorders

Answer 38

1) Alcohol
2) Hypothyroidism
3) Drug: Phenytoin, Li, amiodarone
4) Genetic