Introduction to Parkinson's Disease

Question 1

Define Parkinson’s Disease.

Answer 1

It is a chronic, progressive neurodegenerative disease which is characterised by movement disorders as a result of loss of dopaminergic neurons within the substantia nigra.

Question 2

What is the prevalence of Parkinson’s disease in the UK?

Answer 2

It affects 137,000 people in the UK equivalent to 1/37.

Question 3

Is Parkinson’s the most common neurodegenerative disease?

Answer 3

No it is the 2nd most common neurodegenerative disease after Alzheimer’s.

Question 4

Which gender has a higher prevalence of Parkinson’s?

Answer 4

Men have a slightly higher incidence compared to women.

Question 5

At what age do symptoms of Parkinson’s tend to appear?

Answer 5

Average age of diagnosis is around the age of 60.
People diagnosed with Parkinson’s below the age of 50 is known as young onset Parkinson’s disease.
1/20 are diagnosed before the age of 40.

Question 6

What are some of the motor symptoms of Parkinson’s (known as the classic triad)?

Answer 6

Bradykinesia
Muscle rigidity
Tremour

Question 7

What are some of the non-motor symptoms of Parkinson’s?

Answer 7

Depression/Anxiety
Fatigue
Cognitive impairment
Sleep disturbance
Constipation
Hyposmia (decreased sensation of smell)
Sialorrhoea (excessive production of saliva, drooling)
Excessive sweating
Urinary/bladder problems
Pain
Hypotension

Question 8

What is Parkinsonism?

Answer 8

Parkinsonism is an umbrella term used to cover a range of conditions that share similar symptoms to Parkinson’s - usually the classic triad bradykinesia, muscle rigidity and tremour.

Question 9

What are the three types of Parkinsonism?

Answer 9

Idiopathic Parkinsonism: which is Parkinson’s disease, this is the most common type.

Vascular Parkinsonism: also known as arteriosclerotic parkinsonism, is caused by a restricted blood supply to the brain and often occurs following a mild stroke. Symptoms can include problems with memory, sleep, mood and movement.

Drug-induced Parkinsonism: Neuroleptic drugs (used to treat schizophrenia and other psychotic disorders), which block the action of the chemical dopamine in the brain, are thought to be the biggest cause of drug-induced parkinsonism.

The symptoms of drug-induced parkinsonism tend to stay the same – only in rare cases do they progress in the way Parkinson’s disease does, most recover within months - often within days or weeks.

Question 10

Does symptoms of drug-induced Parkinsonism progress similarly to PD?

Answer 10

It is usually very rare for the symptoms to progress, most recover within months - but most within days or weeks.

Question 11

What is the dopaminergic pathway most associated with Parkinson’s disease?

Answer 11

Whilst loss of dopaminergic neurons affects all pathways the most associated with Parkinson’s disease is the nigrostriatal pathway which connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (caudate nucleus and putamen) in the forebrain. This pathways is the first to experience the effects of loss of dopaminergic neurons and is responsible for the initial motor symptoms displayed in the disease.

Neuronal changes in other dopaminergic pathways and non-dopaminergic pathways are responsible for non-motor symptoms.

Question 12

Which neuronal pathways are responsible for the behavioural effects in PD?

Answer 12

Mesolimbic and mesocortical pathways

Question 13

Which neuronal pathways are responsible for the endocrine control in PD?

Answer 13

Tuberohypophyseal system projects in the pituitary gland, affecting the endocrine control

Question 14

What is bradykinesia?

Answer 14

Bradykinesia is the slowness of voluntary movement which can be assymetrical and unpredictable.

Question 15

How does bradykinesia present in patients?

Answer 15

Limited expression, and blink less frequently
Hypophonia, having a soft voice
Micrographia, small handwriting
Difficulty performing fine motor symptoms such as tying laces and buttoning up shirts
Walking with a shuffling gait

Question 16

Which muscles are most affected by increased rigidity as seen in Parkinson’s disease?

Answer 16

The flexor muscles of the trunk and limbs, this is any muscle responsible for decreasing an angle between two joints.
This includes the elbow and the knee.

Question 17

How does rigidity present in patients?

Answer 17

Rigidity in these flexor muscles produces the characteristic stopping posture of Parkinson’s disease.
This increases the risk of falls, especially due to bradykinesia as there is reduced reaction time.
Patients may also complain of muscle pain.

Question 18

How does tremour present in patients?

Answer 18

Usually occurs at rest and improves with voluntary movement or with mental concentration
Can present in one or both hands with a pill-rolling motion as if a pill is being rolled between the thumb and forefinger
It can also affect the chin, lips, face and legs

Question 19

Do all patients with Parkinson’s experience a tremour?

Answer 19

No not all patients with PD will experience a tremour and equally not all tremours are caused by Parkinson’s.

Question 20

What are some of the other potential causes of tremours?

Answer 20

Certain medicines.
Brain, nerve, or movement disorders, including uncontrolled muscle movements (dystonia)
Brain tumours
Alcohol use or alcohol withdrawal
Multiple sclerosis
Muscle tiredness or weakness
Normal ageing
Overactive thyroid (hyperthyroidism)

Question 21

List some of the medications known to cause tremour as side effects (inducing Parkinsonism).

Answer 21

Antiarrhythmics
Antibiotics/Antivirals
Antidepressants
Antiepileptics
Bronchodilators (B2 agonists)
Chemotherapeutics
Drugs of misuse
GI drugs (Cimetidine and Metoclopramide)
Hormones
Immunosuppressants
Methylxanthines
Neuroleptics/dopamine depletors

Question 22

Which anti-psychotics are known to cause tremour?

Answer 22

More commonly 1st generation anti-psychotics such as haloperidol and are less common in the second generation anti-psychotics such as Clozapine and Olanzapine.

Question 23

When do the extra-pyramidal side effects associated with anti-psychotics occur?

Answer 23

Usually occur within the first 20 weeks of treatment.
They are dose-dependent and are reversible

Question 24

Define extra-pyramidal side effects.

Answer 24

Also known as drug-induced movement disorders, with extra-pyramidal defined as causing involuntary movement you are unable to control - muscle contractions.

Question 25

Which anti-emetics are known to cause extra-pyramidal side effects?

Answer 25

Metoclopramide Prochlorperazine

Question 26

Which other prescription medication can cause Parkinsonism symptoms?

Answer 26

Reserpine (anti-HTN) and Tetrabenzine (involved in involuntary movement disorders) both deplete monoamines, stopping dopamine release.

Question 27

Which recreational drug can cause Parkinsonism?

Answer 27

MPTP (contaminant of synthetic heroin) can destroy dopaminergic neurons within the substantia nigra causing sudden and irreversible Parkinsonism's.

Question 28

What is the most common risk factor for Parkinson's?

Answer 28

Age

Question 29

What percentage of patients with Parkinson's disease have identified inherited genes?

Answer 29

10%

Question 30

What are the three genes are associated with PD?

Answer 30

a-synuclein point mutation Lewy body accumulation Parkin gene mutation

Question 31

Are mutations in the a-synuclein genes acquired or inherited?

Answer 31

Mutations in a-synuclein leading to the development of PD can be either acquired or inherited. The inherited mutation is autosomal dominant and leads to earlier onset PD.

Question 32

What is a-synuclein responsible for?

Answer 32

Although its function is poorly understood it is believed it has a role in brain plasticity and neurotransmitter release.

Question 33

What happens when there are mutations in the SNCA gene that encodes a-synuclein?

Answer 33

Mutations in the SNCA gene results in the misfolding of the protein leading to aggregation and damage to intracellular components. The aggregation process of α-Synuclein involves a conformational change whereby it adopts a β-sheet-rich structure that facilitates its aggregation into oligomers, protofibrils, and insoluble fibrils that finally accumulate in Lewy bodies. Misfolded a-synuclein and Lewy bodies then proceed to cause death of neuronal cell bodies.

Question 34

Which mutations are responsible for autosomal recessive early onset of Parkinson's?

Answer 34

Mutations in the Park-2 gene which encodes parkin a neuroprotective enzymatic protein involved in mitochondrial quality control. However it also protects against the toxic effects of a-synuclein resulting in neuronal cell body damage and cell death.

Question 35

What are the physical causes of Parkinson's?

Answer 35

Dementia pugillistica which causes late onset Parkinson's and dementia. This is caused by physical repeated injuries to the brain such as concussions. Other injuries to the dopaminergic system including head and brainstem injuries and stroke (cerebral ischaemia).

Question 36

What are the viral infection that is associated with Parkinsonism?

Answer 36

Encephalitis Lethargica causing severe Parkinson's and for the patient to 'seize up'. Short-term relief was provided by Levodopa.

Question 37

How should patients first presenting with symptoms of Parkinson's be managed?

Answer 37

Usually patients will present in primary care, and as Parkinson symptoms appear gradually it may be after a significant period of time since the first symptoms were present. If Parkinson's are suspected in any patients, they should be referred urgently to a specialist untreated.

Question 38

How is the diagnosis of Parkinson's made?

Answer 38

Based upon symptoms, medical history and detailed neurological examination. As there are no specific tests used to confirm the diagnosis If there is an improvement of symptoms with the administration of Parkinson's medications

Question 39

Which scans may be used in the diagnosis of Parkinson's?

Answer 39

MRI - however only used to exclude differential diagnosis DaTSCAN - which measures the density of the nigrostriatal dopamine transporter sites - however is not NICE recommended

Question 40

What is the criteria required for diagnosis of Parkinson's syndrome?

Answer 40

Bradykinesia and at least one of the following: Muscular rigidity Rest tremour (4-6 Hz) Postural instability

Question 41

What is the exclusion criteria for Parkinson's?

Answer 41

Repeated strokes with stepwise progression Repeated head injury Anti-psychotic or dopamine-depleting drugs Definite encephalitis or oculogyric crisis on no drug treatment More than one affected relative Sustained remission Negative response to large response to Levodopa Strictly unilateral features after 3 years Other neurological features Exposure to known neurotoxin Presence of cerebral tumour

Question 42

What is the supportive criteria for Parkinson's disease?

Answer 42

Three or more required for diagnosis: Unilateral onset Excellent response to Levodopa Rest tumour present Severe Levodopa induced chorea Progressive disorder Levodopa response over 5 years Persistent asymmetry affecting the side of onset most Clinical course over 10 years