Introduction to Parkinson's Disease Flashcards

1
Q

Define Parkinson’s Disease.

A

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.

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2
Q

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

A

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

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3
Q

Is Parkinson’s the most common neurodegenerative disease?

A

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

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4
Q

Which gender has a higher prevalence of Parkinson’s?

A

Men have a slightly higher incidence compared to women.

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5
Q

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

A

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.

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6
Q

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

A

Bradykinesia
Muscle rigidity
Tremour

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7
Q

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

A

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

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8
Q

What is Parkinsonism?

A

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.

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9
Q

What are the three types of Parkinsonism?

A

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.

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10
Q

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

A

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

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11
Q

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

A

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.

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12
Q

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

A

Mesolimbic and mesocortical pathways

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13
Q

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

A

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

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14
Q

What is bradykinesia?

A

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

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15
Q

How does bradykinesia present in patients?

A

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

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16
Q

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

A

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.

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17
Q

How does rigidity present in patients?

A

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.

18
Q

How does tremour present in patients?

A

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

19
Q

Do all patients with Parkinson’s experience a tremour?

A

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

20
Q

What are some of the other potential causes of tremours?

A

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)

21
Q

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

A

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

22
Q

Which anti-psychotics are known to cause tremour?

A

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

23
Q

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

A

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

24
Q

Define extra-pyramidal side effects.

A

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

25
Q

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

A

Metoclopramide
Prochlorperazine

26
Q

Which other prescription medication can cause Parkinsonism symptoms?

A

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

27
Q

Which recreational drug can cause Parkinsonism?

A

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

28
Q

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

A

Age

29
Q

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

A

10%

30
Q

What are the three genes are associated with PD?

A

a-synuclein point mutation
Lewy body accumulation
Parkin gene mutation

31
Q

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

A

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.

32
Q

What is a-synuclein responsible for?

A

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

33
Q

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

A

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.

34
Q

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

A

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.

35
Q

What are the physical causes of Parkinson’s?

A

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).

36
Q

What are the viral infection that is associated with Parkinsonism?

A

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

37
Q

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

A

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.

38
Q

How is the diagnosis of Parkinson’s made?

A

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

39
Q

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

A

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

40
Q

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

A

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

41
Q

What is the exclusion criteria for Parkinson’s?

A

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

42
Q

What is the supportive criteria for Parkinson’s disease?

A

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