Parkinson's Disease

Question 1

PD is an example of what type of movement disorder? Is this pyramidal or extrapyramidal?

Answer 1

Hypokinetic / extrapyramidal

Question 2

Which part of the brain is affected in PD?

Answer 2

Basal ganglia

Question 3

What specific part of the basal ganglia is affected in PD?

Answer 3

The pars compacta region of the substantia nigra

Question 4

What is the key pathological feature of PD?

Answer 4

Loss of dopaminergic neurones in the substantia nigra

Question 5

Sections through the brainstem in a PD sufferer would show what? What does this correlate with?

Answer 5

Loss of the normally dark black pigment of the substantia nigra / correlates with dopaminergic cell loss

Question 6

Symptoms of PD generally do not tend to show until there is what?

Answer 6

Loss of around 60% of neurones in the substantia nigra

Question 7

The neurones which remain in the substantia nigra in PD can often accumulate what? Within where?

Answer 7

The protein alpha-synuclein within Lewy bodies

Question 8

What are Lewy bodies?

Answer 8

Abnormal aggregates of protein that develop inside nerve cells

Question 9

In terms of describing the pathophysiology of PD, the degeneration of dopaminergic neurones in the substantia nigra are associated with what? Which leads to what?

Answer 9

A decrease in dopamine levels which leads to increased basal ganglia inhibitory output and hypokinetic symptoms

Question 10

What are the risk factors for developing PD?

Answer 10

Increasing age, male gender, family history, other environmental/genetic factors

Question 11

What feature increases the probability of a genetic cause for PD?

Answer 11

Early onset, particularly < 40 years

Question 12

A mutation in the PARK2 gene is responsible for causing what?

Answer 12

Typical, early onset (< 50 years) PD

Question 13

A mutation in the ATP13A2 gene is responsible for causing what?

Answer 13

Atypical, juvenile onset (children/teens) PD

Question 14

Around 50% of patients with PD aged < 50 have a mutation in which gene?

Answer 14

PARK2

Question 15

LRRK2 and SNCA are both genes in which mutations can lead to PD. How are these inherited?

Answer 15

Autosomal dominant

Question 16

PARKIN and PINK1 are both genes in which mutations can lead to PD. How are these inherited?

Answer 16

Autosomal recessive

Question 17

What are the 3 main groups of symptoms of PD?

Answer 17

Hypokinetic motor symptoms, hyperkinetic motor symptoms and non-motor symptoms

Question 18

What are the 3 main hypokinetic motor symptoms of PD?

Answer 18

Bradykinesia/akinesia, rigidity and postural instability

Question 19

The rigidity in PD is often described as what?

Answer 19

Cogwheeling

Question 20

Rigidity is a feature of PD which can cause what?

Answer 20

A stooped posture and an expressionless ‘mask like’ face

Question 21

Which of the 3 main hypokinetic motor features of PD usually develops last? This can often lead to what?

Answer 21

Postural instability, often leads to falls

Question 22

What is the only hyperkinetic motor feature of PD?

Answer 22

Resting tremor

Question 23

What are the 4 main non-motor features which can be seen in PD?

Answer 23

Hyposmia/anosmia, sleep disorders, depression/psychosis/dementia, autonomic features

Question 24

What are some examples of autonomic features which may be seen in PD?

Answer 24

GI/bladder dysfunction, postural hypotension

Question 25

Motor features in PD are heterogenous, but what are the two broad subtypes?

Answer 25

Tremor dominant (with relative absence of other features) and non-tremor dominant

Question 26

What are the outcomes of tremor dominant PD when compared with non-tremor dominant PD?

Answer 26

Slower rate of progression and less functional disability

Question 27

How do the motor symptoms of PD usually start?

Answer 27

They usually start asymmetrically, often as a resting tremor in one arm

Question 28

In PD, what tends to come first - motor or non-motor symptoms?

Answer 28

Non-motor

Question 29

Essential Parkinsonism can be defined as bradykinesia and at least one of what other features?

Answer 29

Resting tremor, postural instability or rigidity

Question 30

What are some additional motor features of PD which are not included in the criteria for essential Parkinsonism?

Answer 30

Stooped, fixed or dystonic posture, hypomimia (masked face), shuffling gait

Question 31

What is cogwheel rigidity?

Answer 31

A superimposed clicking resistance, often attributed to the underlying tremor

Question 32

What is lead pipe rigidity?

Answer 32

Constant resistance throughout passive movement

Question 33

Idiopathic PD is diagnosed how?

Answer 33

It is a diagnosis of exclusion

Question 34

Idiopathic PD is a clinical diagnosis and can be confirmed with what?

Answer 34

Essential Parkinsonism, no alternative explanation for symptoms (e.g. drugs), responsiveness to Levodopa

Question 35

Before diagnosing idiopathic PD, what should you exclude?

Answer 35

Treatable causes of asthenia e.g. anaemia or hypothyroidism

Question 36

Does tremor occur in all patients with PD?

Answer 36

No, around 70%

Question 37

Patients with idiopathic PD should NOT present with what?

Answer 37

Early onset bulbar problems, dementia/hallucinations, eye movement disorder or intrusive autonomic features

Question 38

What is a useful test to do to diagnose PD and why?

Answer 38

Idiopathic PD usually responds to treatment with Levodopa, so a trial of this to see if there is an improvement in symptoms is a good test to do

Question 39

What test can be done to visualise neurodegeneration in the basal ganglia in PD?

Answer 39

MRI

Question 40

What test can be done to assess dopamine levels in the basal ganglia in PD?

Answer 40

SPECT

Question 41

In PD, symptomatic treatments are used to do what?

Answer 41

Enhance intracerebral dopamine or stimulate dopamine receptors

Question 42

What is the main symptomatic drug for PD and what is its mechanism of action?

Answer 42

Levodopa - a dopamine precursor

Question 43

What is the 2nd line symptomatic drug group for PD? What are some examples?

Answer 43

Dopamine agonists - apomorphine, ropinirole and pramipexole

Question 44

What are some last line symptomatic drug treatments for PD?

Answer 44

Monoamine oxidase type B inhibitors and amantadine

Question 45

Why is dopamine itself not used to treat PD?

Answer 45

Because it does not cross the BBB

Question 46

When should treatment for PD be initiated?

Answer 46

When symptoms are causing discomfort and disability

Question 47

Which symptoms of PD respond reliably to dopaminergic treatment in early disease?

Answer 47

Bradykinesia and rigidity

Question 48

Which symptom of PD is inconsistently responsive to dopaminergic treatment?

Answer 48

Resting tremor

Question 49

What can be an effective treatment for tremor in PD?

Answer 49

Anticholinergic agents e.g. trihexyphenidyl

Question 50

What are some non-oral therapies that can be used for PD?

Answer 50

Continuous apomorphine infusions and deep brain stimulation

Question 51

Dopamine agonists and Levodopa are associated with what side effects?

Answer 51

Nausea, daytime somnolence and oedema

Question 52

Dopamine agonists can cause what kind of disorders?

Answer 52

Impulse control disorders

Question 53

Dopamine agonists should not be prescribed in who?

Answer 53

Patients with a history of addiction/OCD/impulsive personalities and the elderly (especially with cognitive impairment)

Question 54

Which drug used to treat PD has the greatest symptomatic benefit? What are its downsides?

Answer 54

Levodopa / associated with motor complications (dyskinesias) and reduced effect after 5-10 years

Question 55

Younger patients with PD are often started on which drug first?

Answer 55

Dopamine agonists

Question 56

What are the main long term complications of dopaminergic therapies for PD?

Answer 56

Motor and non-motor fluctuations, dyskinesias, psychosis

Question 57

What are motor/non-motor fluctuations?

Answer 57

Alterations between periods of good motor/non-motor symptom control and periods of reduced motor/non-motor symptom control

Question 58

Which dyskinesias are most likely to be caused by Levodopa? They tend to occur when?

Answer 58

Involuntary chorieform or dystonic movements / when levodopa concentrations are at maximum

Question 59

What is it known as if involuntary dyskinesias occur at the beginning or the end of a levodopa dose?

Answer 59

Diphasic dyskinesia

Question 60

What type of hallucinations are most likely to occur in PD?

Answer 60

Visual

Question 61

What problems with regards to sleep can be seen in PD?

Answer 61

REM sleep disorders and restless legs