Neurology: Parkinson's & Benign Essential Tremor

Question 1

Give some causes of Parkinsonism?

Answer 1

1) Parkinson’s disease

2) Drugs e.g. antipsychotics, metoclopramide

3) Progressive supranuclear palsy

4) multiple system atrophy

5) Wilson’s disease

6) post-encephalitis

7) dementia pugilistica (secondary to chronic head trauma e.g. boxing)

8) toxins: carbon monoxide, MPTP

Question 2

What is Parkinson’s disease (PD)?

Answer 2

A progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra.

Question 3

What triad of features is seen in PD?

Answer 3

he reduction in dopaminergic output results in a classical triad of features:

1) Bradykinesia
2) Tremor
3) Rigidity

Question 4

Are the symptoms of PD characteristically symmetrical or asymmetrical?

Answer 4

Asymmetrical

Question 5

Mean age of PD diagnosis?

Answer 5

65y

Question 6

Is PD more common in men or women?

Answer 6

2x more common in men

Question 7

What is bradykinesia?

How may it typically present?

Answer 7

Slowness of movement:

• Small steps when walking (“shuffling” gait) with reduced arm swinging
• Handwriting gets smaller and smaller (micrographia)
• Difficulty in initiating movement (e.g., going from standing still to walking)
• Rapid frequency of steps to compensate for the small steps and avoid falling (“festinating” gait)

Question 8

What is the frequency of the tremor in PD?

Answer 8

3-5 Hertz

Question 9

Describe the tremor seen in PD

Answer 9

• typically ‘pill-rolling’, i.e. in the thumb and index finger
• worse when stressed or tired
• improves with voluntary movement

Question 10

When is the tremor in PD most marked?

Answer 10

At rest

Question 11

When does the tremor in PD improve?

Answer 11

With voluntary movement

Question 12

What makes the tremor in PD get worse?

Answer 12

• Stressed or tired
• When the patient is distracted: e.g. Performing a task with the other hand (e.g., miming the act of painting a fence) exaggerates the tremor.

Question 13

What is rigidity?

Answer 13

Rigidity is resistance to the passive movement of a joint.

Question 14

How to test rigidity in PD?

Answer 14

Taking a hand and passively flexing and extending the arm at the elbow demonstrates tension in the arm that gives way to movement in small increments (like little jerks).

Question 15

What are the 2 types of ridigity that can be seen in PD?

Answer 15

1) Cogwheel rigidity
2) Leadpipe rigidity

Question 16

Cogwheel vs leadpipe rigidity?

Answer 16

Cogwheel - a combination of lead-pipe rigidity with tremor, jerking resistance to movement

Leadpipe - a constant resistance to motion throughout the entire range of movement.

Question 17

Other features seen in PD?

Answer 17

1) Reduced facial movements and facial expressions (hypomimia)

2) Depression (affects about 40%)

3) Sleep disturbance and insomnia

4) Anosmia

5) Postural instability (increasing the risk of falls)

6) Cognitive impairment and memory problems

7) Drooling of saliva

Question 18

Parkinson’s tremor vs benign essential tremor:

a) symmetry
2) frequency
3) better/worse at rest
4) better/worse with intentional movement
5) other Parkinson’s features
6) change with alcohol

Answer 18

PD tremor:
a) asymmetrical
2) 3-5 Hz
3) worse at rest
4) better with intentional movement
5) other Parkinson’s features
6) no change with alcohol

Benign essential tremor:
a) symmetrical
b) 6-12 Hz
3) better at rest
4) worse with intentional movement
5) no other Parkinson’s features
6) improves with alcohol

Question 19

Describe features of drug-induced parkinsonism vs features of PD

Answer 19

Drug-induced parkinsonism has slightly different features to Parkinson’s disease:

1) motor symptoms are generally rapid onset and bilateral

2) rigidity and rest tremor are uncommon

Question 20

If there is difficulty differentiating between essential tremor and PD, what investigation can be considered?

Answer 20

I‑FP‑CIT single photon emission computed tomography (SPECT).

Question 21

What is multiple system atrophy?

Answer 21

A rare condition where the neurones of various systems in the brain degenerate, including the basal ganglia.

Question 22

Features of multiple system atrophy?

Answer 22

1) Parkinsonism features

2) Autonomic dysfunction: causing postural hypotension, constipation, abnormal sweating and sexual dysfunction

3) Cerebellar dysfunction: causing ataxia

Question 23

What is dementia with lewy bodies?

Answer 23

A type of dementia associated with features of Parkinsonism.

Question 24

Associated symptoms in dementia with lewy bodies?

Answer 24

1) Parkinsonism
2) visual hallucinations
3) delusions
4) REM sleep disorders
5) fluctuating consciousness.

Question 25

4 groups of treatment options in PD?

Answer 25

1) Levodopa (combined with peripheral decarboxylase inhibitors)

2) COMT inhibitors

3) Dopamine agonists

4) Monoamine oxidase-B inhibitors

Question 26

What is Levodopa?

Answer 26

A synthetic dopamine taken orally.

Question 27

What is levodopa usually combined with?

Answer 27

a peripheral decarboxylase inhibitor (e.g., carbidopa and benserazide)

Question 28

Give 2 examples of peripheral decarboxylase inhibitors

Answer 28

1) carbidopa
2) benserazide

Question 29

Purpose of combining levadopa with a peripheral decarboxylase inhibitor?

Answer 29

stops it from being metabolised in the body before it reaches the brain.

Question 30

1st line treatment option in PD if the motor symptoms are affecting the patient’s quality of life?

Answer 30

Levodopa

Question 31

1st line treatment in PD if the motor symptoms are not affecting the patient’s quality of life?

Answer 31

Aopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor

Question 32

Which class of drug in PD provides the most improvement in motor symptoms?

Answer 32

Levodopa

Question 33

What are 2 combination drugs given in PD? (i.e. levodopa + peripheral decarboxylase inhibitor)?

Answer 33

1) Co-beneldopa (levodopa and benserazide), with the trade name Madopa

2) Co-careldopa (levodopa and carbidopa), with the trade name Sinemet

Question 34

What is the main side effect of levodopa?

Answer 34

Dyskinesia (abnormal movements associated with excessive motor activity)

Question 35

Give 3 examples of dyskinesia that may be seen in levodopa use

Answer 35

1) Dystonia (where excessive muscle contraction leads to abnormal postures or exaggerated movements)

2) Chorea (abnormal involuntary movements that can be jerking and random)

3) Athetosis (involuntary twisting or writhing movements, usually in the fingers, hands or feet)

Question 36

What may be given to manage dyskinesia associated with levodopa?

Answer 36

Amantadine (a glutamate antagonist)

Question 37

What are COMT inhibitors?

Answer 37

inhibitors of catechol-o-methyltransferase (COMT).

Question 38

Give an example of a COMT inhibitor used in PD

Answer 38

entacapone

Question 39

What is the role of the COMT enzyme?

Answer 39

The COMT enzyme metabolises levodopa in both the body and brain.

Question 40

Purpose of giving COMT inhibitor (e.g. entacapone) in PD?

Answer 40

Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow the breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.

Question 41

Give 3 examples of dopamine agonists used in PD

Answer 41

1) Bromocriptine
2) Pergolide
3) Cabergoline

Question 42

Levodopa vs dopamine agonists in PD?

Answer 42

Dopamine agonists are less effective than levodopa in reducing symptoms.

Question 43

When are dopamine agonists typically used in PD?

Answer 43

They are typically used to delay the use of levodopa, then used in combination with levodopa to reduce the required dose.

Question 44

What is a notable side effect of prolonged use of dopamine agonists?

Answer 44

Pulmonary fibrosis

Question 45

What are Monoamine oxidase-B inhibitors?

Answer 45

Monoamine oxidase-B inhibitors block the action of monoamine oxidase-B enzymes, helping to increase the circulating dopamine.

Question 46

Use of monoamine oxidase-B inhibitors in PD?

Answer 46

Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. Monoamine oxidase-B is more specific to dopamine.

They are typically used to delay the use of levodopa, then in combination with levodopa to reduce the “end of dose” worsening of symptoms.

Question 47

Give 2 examples of Monoamine oxidase-B inhibitors used in PD?

Answer 47

1) Selegiline
2) Rasagiline

Question 48

PD medication can be associated with impulse control disorders.

These can occur with any dopaminergic therapy but are more common which which class of drug?

Answer 48

Dopamine agonists

Question 49

What are 2 risk factors for a patient developing an impulse control disorder on PD medication?

Answer 49

1) a history of previous impulsive behaviours

2) a history of alcohol consumption and/or smoking

Question 50

Common side effects of levodopa?

Answer 50

dry mouth
anorexia
palpitations
postural hypotension
psychosis

Question 51

Some adverse effects are due to the difficulty in achieving a steady dose of levodopa.

Give some examples:

Answer 51

1) End-of-dose wearing off: symptoms often worsen towards the end of dosage interval, which results in a decline of motor activity

2) ‘On-off’ phenomenon: large variations in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period

3) Dyskinesias at peak dose: dystonia, chorea and athetosis (involuntary writhing movements)

Question 52

What is reason for not acutely stopping levodopa (e.g. if patient is admitted to hospital)?

Answer 52

if a patient with Parkinson’s disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia

Question 53

What class of drug is used to treat drug-induced parkinsonism?

Answer 53

Anticholinergics e.g. Procyclidine

Question 54

What is a benign essential tremor?

Answer 54

It is characterised by a fine tremor affecting all the voluntary muscles.

A relatively common condition associated with older age.

Question 55

Features of benign essential tremor?

Answer 55

• Tremor most notable in hands

Can affect other areas:
- Head tremor
- Jaw tremor
- Vocal tremor

Question 56

describe the tremor in benign essential tremor

Answer 56

1) Fine tremor (6-12 Hz)

2) Symmetrical

3) More prominent with voluntary movement

4) Worse when tired, stressed or after caffeine

5) Improved by alcohol

6) Absent during sleep

Question 57

What are the key differentials of a tremor?

Answer 57

1) PD

2) Benign essential tremor

3) Multiple sclerosis

4) Huntington’s chorea

5) Hyperthyroidism

6) Fever

7) Dopamine antagonists (e.g., antipsychotics)

Question 58

Management for a benign essential tremor?

Answer 58

There is no definitive treatment for benign essential tremor. The tremor is not harmful and does not require treatment if it is not causing functional or psychological problems.

Question 59

What are 2 medications that may be used in benign essential tremor?

Answer 59

1) Propranolol (a non-selective beta blocker)

2) Primidone (a barbiturate anti-epileptic medication)

Question 60

What is the role of monoamine oxidase B?

Answer 60

Monoamine oxidase-B (MAO-B) is an enzyme in the body that breaks down several chemicals in the brain, including dopamine.