Parkinsonian Disorders

Question 1

What are Parkinsonian disorders?

Answer 1

Disorders of movement divide broadly into two categories:

1. Hypokinesias – characterised by slowed movements with increased tone (Parkinsonism)
2. Hyperkinesias – excessive involuntary movements.

Both types may co-exist

Question 2

What is Parkinsons disease?

Answer 2

Parkinson’s disease is a progressive nervous system disorder that affects movement. Symptoms start gradually, sometimes starting with a barely noticeable tremor in just one hand. Tremors are common, but the disorder also commonly causes stiffness or slowing of movement.

Question 3

What causes Parkinsons disease?

Answer 3

1. Age and gender (>70 years, more in men)
2. Environmental factors (Pesticide exposure, MPTP)
3. Genetic factors (Significant genetic component in early-onset PD)

Question 4

What is the gender bias of Parkinsons disease?

Answer 4

M:F –> 1.5:1

Question 5

What is the prevalence of Parkinsons disease in those over 80?

Answer 5

1 in 200

Question 6

What are the two pathological hallmarks of Parkinsons disease?

Answer 6

1. The presence of Lewy bodies

2. Loss of the dopaminergic neurones

Question 7

What do you know about the Lewy bodies in Parkinsons disease?

Answer 7

Lewy bodies contain tangles of α- synuclein and ubiquitin and become gradually more widespread as the condition progresses

Spreads from lower brainstem to midbrain and then cortex

Question 8

In Parkinsons disease, where is the main loss of dopaminergic neurones?

Answer 8

Loss of the dopaminergic neurones from the pars compacta of the substantia nigra in the midbrain that project to the striatum of the basal ganglia

Question 9

How does Parkinsons disease typically present?

Answer 9

PD almost always presents with the typical motor symptoms of tremor and slowness of movement but it is likely that the pathological process starts many years before these symptoms develop

Question 10

What percentage of dopaminergic neurons are lost at the initial presentation of Parkinsons disease?

Answer 10

By the time of first presentation, on average 70% of dopaminergic nigrostriatal cells have already been lost.

Question 11

What are the Prodromal premotor symptoms in Parkinsons disease?

Answer 11

1. Anosmia (present in 90%) – the olfactory bulb is one of the first structures to be affected
2. Depression and anxiety (50%)
3. Aches and pains
4. REM sleep behaviour disorder
5. Autonomic features – urinary urgency, hypotension
6. Constipation
7. Restless leg syndrome

Question 12

What are the motor symptoms in Parkinsons disease?

Answer 12

1. Akinesia
2. Tremor
3. Rigidity
4. Postural and gait disturbance

Question 13

How is the akinesia in Parkinsons disease characterised?

Answer 13

Poverty/slowing of movement - a cardinal clinical feature and main cause of disability

1. Difficulty initiating movement, usually in upper limbs first (unilateral); especially dexterous movements
2. Facial immobility: lack of expressions and lack of blinking

Question 14

How would you test for akinesia in Parkinson disease?

Answer 14

Akinesia is tested for clinically by asking the patient to perform rapid alternating movements such as opening and closing the hand repetitively or pronating and supinating the arm, looking for progressive slowing and decrement in amplitude of movement.

Question 15

How is the tremor in Parkinsons disease characterised?

Answer 15

The presenting symptom in 70% of patients

• Almost always starts in the fingers and hand and like akinesia, is unilateral initially
• The tremor is present at rest and reduces or stops completely when the hand is in motion
• The frequency is 3–6 Hz and it is often described as pill-rolling because the patient appears to be rolling something between thumb and forefinger
• As with most tremors it is made worse by emotion or stress.

Question 16

How is the rigidity in Parkinsons disease characterised?

Answer 16

• Stiffness on passive limb movement is described as ‘lead pipe’ as it is present throughout the range of movement and unlike spasticity
• When stiffness occurs with tremor (not always visible), a ratchet-like jerkiness is felt, described as cogwheel rigidity

Question 17

How are the postural and gait disturbances in Parkinsons disease characterised?

Answer 17

• A stooped posture is characteristic. Gait gradually becomes shuffling with small stride length, slow turns, freezing and reduced arm swing
• Postural stability eventually deteriorates, leading to falls, but this is a late stage feature which should arouse suspicion of an alternative diagnosis if present during the first 5 years

Question 18

How does cognition relate to Parkinson’s disease?

Answer 18

Cognitive impairment is now recognised to be common in late stage PD (80%) and may develop into dementia.

Visual hallucinations on treatment, and psychosis are not uncommon, and may herald evolving cognitive decline

Question 19

How would you diagnose Parkinson’s disease?

Answer 19

No specific test exists to diagnose

Suspect Parkinson’s disease in people presenting with tremor, stiffness, slowness, balance problems and/or gait disorders

If Parkinson’s disease is suspected, refer people quickly and untreated to a specialist with expertise in the differential diagnosis of this condition

Question 20

How would you manage Parkinson’s disease?

Answer 20

1. Offer levodopa to people in the early stages of Parkinson’s disease whose motor symptoms impact on their quality of life
2. Consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO‑B) inhibitors for people in the early stages of Parkinson’s disease whose motor symptoms do not impact on their quality of life

Question 21

What is the mechanism of action of levodopa?

Answer 21

Levodopa is converted to dopamine via the action of a naturally occurring enzyme called DOPA decarboxylase. This occurs both in the peripheral circulation and in the central nervous system after levodopa has crossed the blood brain barrier.

Activation of central dopamine receptors improves the symptoms of Parkinson’s disease

Question 22

What drugs classes can induce Parkinsonism?

Answer 22

neuroleptics (antipsychotics)
dopamine depleting drugs.
antiemetics.
calcium-channel blockers.

Question 23

What antipsychotics can cause Parkinsonism?

Answer 23

fluphenazine
chlorpromazine
promazine
pimozide
haloperidol
perphenazine

Question 24

What is the most effective drug for Parkinson’s disease?

Answer 24

Levodopa

It is usually well tolerated and adverse effects (nausea and dizziness) are quite rare and mild.

Question 25

What drug is levodopa usually given with?

Answer 25

It is given with a peripheral dopa-decarboxylase inhibitor, which prevents peripheral conversion to dopamine and prevents side-effects like nausea

Question 26

When would you choose Dopamine agonists instead of levodopa in Parkinson’s disease?

Answer 26

In the long term they are associated with fewer dyskinesia and motor fluctuations compared with levodopa and may therefore be more appropriate for use in younger patients

They are less effective than levodopa, and levodopa is eventually required.

Question 27

What would you do about hallucinations and delusions in Parkinson’s disease?

Answer 27

Do not treat hallucinations and delusions if they are well tolerated.

Consider quetiapine to treat hallucinations and delusions. If standard treatment is not effective, offer clozapine

Question 28

What medications cause hypersalivation?

Answer 28

Hypersalivation has been reported as a side effect of atypical antipsychotics such as clozapine and olanzapine

Question 29

How would you manage drooling in Parkinsons disease?

Answer 29

Only consider pharmacological management if non-pharmacological management is not available or has not been effective.

Consider glycopyrronium bromide

Question 30

What is Parkinson’s crisis?

Answer 30

Acute akinesia: a rare but life-threatening complication of Parkinson’s disease, with a sudden worsening of motor symptoms and severe akinesia.

Question 31

What are COMT inhibitors? And why are they used in Parkinson’s disease?

Answer 31

Used in more advanced disease

Reversibly inhibit the peripheral breakdown of levodopa by the COMT enzyme, increasing the amount available for conversion to dopamine in the brain and reducing fluctuations in plasma levels.

Entacapone should ideally be offered as a combination drug (levodopa carbidopa entacapone)

Question 32

A 75 year old woman has poorly controlled Parkinson’s disease, for which she takes co-careldopa four times daily. She finds that her symptoms deteriorate before her next dose of medication is due.

Which class of drug would be most appropriate to add to her therapy?

A) Gamma-aminobutyric acid agonist
B) Monoamine oxidase B inhibitor
C) Muscarinic receptor antagonist
D) Noradrenaline (norepinephrine) reuptake inhibitor
E) Serotonin reuptake inhibitor

Answer 32

B) Monoamine oxidase B inhibitor

MAOB inhibitors inhibit dopamine metabolism centrally, therefore prolonging the effect of co-careldopa and extending the alleviation of Parkinsonian symptoms. Stops breakdown of dopamine in cleft to increase dopamine – improving symptoms

Question 33

A 73 year old woman has had nausea since starting co-careldopa for Parkinson’s disease. She takes no other medications and has no known allergies.

Which is the most appropriate antiemetic?

A) Cinnarizine
B) Levomepromazine
C) Metoclopramide
D) Ondansetron
E) Prochlorperazine

Answer 33

Ondansetron

Others have dopaminergic effects and so should not be used in PD.